Article

Comprehensive review on additives of topical dosage forms for drug delivery

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Abstract

Abstract Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

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... Glycerine, hydroxyethyl urea, betaine, sodium-L-lactate, and other humectants are some examples. Humectants are also used in shampoo to help hydrate hair and counter the drying effect of surfactants [7]. They also help with low temperature stabilization and freeze / thaw, acting as antifreeze and maintaining shampoo clarity at low temperatures. ...
... Vitamins are necessary for the proper functioning of the physiological functions of the body and the skin. Vitamins A, B, C, E and others are commonly used in the formulation of the cream [7]. Skincare products contain preservatives to help stop microbe contamination and instability during formulation, shipping, storage, and consumer use. ...
... The diameter of the zone of inhibition for negative control (mm) S. aureus 30 ...
... Herbal soaps in 50 g in weight were formed by adding plant extracts, distilled water, stearic acid and natural volatile oil into the glycerin soap base. However, the active ingredients and added excipients should be compatible with the vehicle 30 . ...
... The skin contributes to around 10% of the net body mass and is mainly composed of three to four layers. The order of the layers is arranged from the peripheral to the profound layers as follows: stratum corneum (SC), viable epidermis and dermis [8,9]. Figure (1.1) schematically illustrates a cross section through human skin layers. ...
... ; VrN=p(6); kve=p(5); kd=p(4); td=p(1); fun = @(s) 1/s/((1/(ClrN+VrN*s*td)+1/kve+1/kd+1/(VdN*s*td))*cosh(sqrt((s)*td))... +(1/sqrt((s)*td)+sqrt((s)*td)*(1/kd+1/(VdN*s*td))*(1/kve+1/(ClrN+VrN*s*td)))... *sinh(sqrt((s)*td))); Jsx=@(s) fun(s); (3)); dose=p (2) (3) 233 j(i)=(n+1)*f(Uk(i,n))*(Uk(i,n)-Uk(i,n+3)/Kr)/(1+(n+1)*f(Uk(i,n))/kve);% w(i)=Uk(i,n+2); end FC=j; ZC=w; end function dy = compartmentDC(y,n,p) td=p(1); VdN=p(3); kd=p(4); kve=p(5); VrN=p(6); ClrN=p(7); Kr=p(8); beta=p(9); f=@(u) exp(beta*u); dy = zeros(n+3,1); dy(n+2)=(n+1)*(f(y(n+2))/(1+(n+1)*f(y(n+2))/kd))*(y(1)-y(n+2))/(VdN*td); % dCv/dt dy(1)=n*(n+1)*(f(y(n+2))/(1+(n+1)*f(y(n+2))/kd)*(y(n+2)-y(1))+(y(2)y(1))*f(y(1)))/td; for i = 2:n-1 dy(i)=n*(n+1)*((y(i-1)-y(i))*f(y(i-1))+(y(i+1)-y(i))*f(y(i)))/td; end dy(n) = n*(n+1)*((y(n-1)-y(n))*f(y(n-1))+f(y(n))/(1+(n+1)*f(y(n))/kve)*(y(n+3)/Kry(n)))/td; dy(n+1)=y(n)*(n+1)*f(y(n))/(1+(n+1)*f(y(n))/kve);% AD/h |(n+1) kp Cn(t) dt = Q dy(n+3)=((n+1)*(f(y(n))/(1+(n+1)*f(y(n))/kve))*(Kr*y(n)-y(n+3))-ClrN*y(n+3))/(VrN*td); (7); Kr=p(8); beta=p (9); f=@(c) exp(beta*c); df=@(c) beta.*exp(beta*c); n=Nfinite; a=(Nfinite-1)^2/td; dy = zeros(n+3,1); dy(n+2)=kd*(y(1)-y(n+2))/(VdN*td); % dCv/dt dy(1)=2*a*f(y(1))*(y(2)-y(1)-(y(1)-y(n+2))*kd/(Nfinite-1)/f(y(1)))... +((y(1)-y(n+2))*kd/f(y(1))).^2*df(y(1))/td; for i = 2:Nfinite-1 dy(i)=a*f(y(i))*(y(i-1)-2*y(i)+y(i+1))+0.25*((Nfinite-1)*(y(i+1)-y(i-1))).^2.*df(y(i))./td; ...
Thesis
Full-text available
In this thesis, we have developed a novel mathematical model using a compartmental approach. The proposed model enables for simulating solute transport across the stratum corneum (SC) in a variety of exposure scenarios in percutaneous drug delivery systems. The obtained results were compared with the diffusion model outcomes – which can be considered the current ‘golden standard’ for modelling skin transport – and showed a good agreement. The mathematical foundations of the model are relatively simple and better aligned with the physiology of the stratum corneum. In addition, this work shows that performing a numerical simulation using the compartmental model is less demanding than using the diffusing model, especially for complex exposure scenarios, and can be performed using free software, such as Python. The research findings of this thesis contribute towards a better understanding of transport phenomena across the skin. Also, the compartmental model proposed in this work can be used to describe transport phenomena in the membrane. Due to the similarity between the governing equations of diffusion and heat transfer, the proposed approach also offers a mathematical framework for studying heat transfer problems in biomaterials with minimum model development or computational efforts.
... The presence of peptidase enzymes, cleave the peptide/protein-based bioactives and limits their bioavailability. Henceforth, prodrug, enzyme inhibitors or novel drug carrier systems are used to protect the bioactives and improve their bioavailability [62]. ...
... Sumatriptan succinate is a 5-HT receptor agonist, commonly prescribed for severe headache and migraine through oral and parenteral route. Though, poor oral bioavailability (15%) due to low permeability through BBB and associated side effects like severe nausea and vomit 62 ing hinders its systemic administration [243,244]. Thus, to improve the bioavailability of sumatriptan succinate in the brain region Galagtte and team (2014) (164.70 %) in the brain via nasal formulation than the oral dosage form. ...
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The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed T organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly fo-cused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery.
... The choice of a specific dosage form is an essential parameter because it can affect the absorption and the bioavailability of the bioactives as a function of interactions that can occur between excipients and biological barriers (i.e., skin, mucosae and intestinal epithelium), and between excipients and bioactives. Different types of dosage forms and excipients can be used to maximize the beneficial effect of bioactives depending on the target, the characteristics of the bioactives, and the administration route (Garg et al., 2015). ...
Article
Plants and their derivates have been used as medicines for centuries and today is being re-discovered their usefulness for the human health. The therapeutic properties of phytochemicals are re-evaluated under the light of medical and pharmacological research, pushed by a constantly growing market demand, where consumers trust more natural products than synthetic drugs. New studies are enlightening the effectiveness of phytochemicals against a wide range of ailments, nevertheless very few evaluate the efficacy of topical formulations based on natural bioactive molecules in the treatment of nasal mucosal diseases. This review aims at exploring this little covered topic. An overview on the properties and functionality of the nasal mucosa and the different diseases affecting it has been provided. We summarized various nasal dosage forms containing natural bioactive and explored how innovative delivery systems loading phytochemicals can improve the treatment results. Finally, the potential use of novel nanocarriers for the treatment of nasal ailments has been covered as well.
... In general, nanotechnology offers a better controlled, nontoxic, more secure and localized delivery of drugs than traditional treatments. A variety of nanotechnology colloidal carriers are popular for treating and controlling psoriasis because of their distinctive characteristics, such as liposomes, niosomes, transmitters, microspheres, micelles, dendrimers, glycosomes, solid lipid nanoparticles, etc. (Figure 3) [70][71][72][73][74][75][76][77][78]. ...
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Psoriasis is a genetic chronic disease mediated by the immune system with systemic and cutaneous manifestations that can significantly deteriorate patients' quality of life. Two-three percent of the population worldwide suffer from psoriasis and it imposes a substantial economic burden on patients. The aetiology is mainly related with genes and environmental factors. The pathophysiology of psoriasis is characterized by T cells and dendritic cells, antimicrobial peptides, genetic predispositions, lipoprotein-2, galactosin-3, fractalkine, vaspin, and human neutrophilic peptides, etc. in the progression of psoriasis. For patients with psoriasis, the traditional treatments include corticosteroids, vitamin D3 analogues, calcineurin inhibitors, methotrexate, cyclosporine, acitretin, phototherapy, and biological agents, etc. Nanodermatology is an emerging, multidisciplinary science that is gaining increasing recognition in the treatment of psoriasis. This review provides a summary of the pathophysiology, epidemiology, clinical diagnosis, and classical pharmacotherapy of psoriasis. The review also summarizes different nanotechnology therapies for effective treatment of psoriasis.
... This allows their non-problematic application by the dentist or by the patient while ensuring the relatively quick release of the drug at the site of application. Their main advantage is a low risk of irritation [112], as well as good rheological properties and good adhesion to differentiated oral mucosa [113]. ...
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The success of modern dental treatment is strongly dependent on the materials used both temporarily and permanently. Among all dental materials, polymers are a very important class with a wide spectrum of applications. This review aims to provide a state-of-the-art overview of the recent advances in the field of natural polymers used to maintain or restore oral health. It focuses on the properties of the most common proteins and polysaccharides of natural origin in terms of meeting the specific biological requirements in the increasingly demanding field of modern dentistry. The use of naturally derived polymers in different dental specialties for preventive and therapeutic purposes has been discussed. The major fields of application cover caries and the management of periodontal diseases , the fabrication of membranes and scaffolds for the regeneration of dental structures, the manufacturing of oral appliances and dentures as well as providing systems for oral drug delivery. This paper also includes a comparative characteristic of natural and synthetic dental polymers. Finally, the current review highlights new perspectives, possible future advancements, as well as challenges that may be encountered by researchers in the field of dental applications of polymers of natural origin.
... In addition, several other excipients/additives such as solvents, co-solvents, surfactants, humectants, thickening agents, and others are used in the development of topical/transdermal formulations. These agents can control the extent of absorption (thermodynamic activity and partition coefficient), maintaining the viscosity and pH, improving the stability as well as the organoleptic properties (Pham et al., 2016;Williams and Barry, 2004;Garg et al., 2015;Brown et al., 2011). Recently, various types of nanodelivery systems have been developed, typically lipid-based, including nanoemulsions and microemulsions (ME), liposomes or flexible vesicles, nanostructured lipid carriers and solid lipid nanoparticles, which can offer the potential to improve bioavailability and efficacy, target delivery to skin regions and follicles, or systemic effectiveness (Ramanunny et al., 2021). ...
Article
Cannabidiol (CBD) is a pleiotropic phytocannabinoid, recently investigated to treat many skin diseases. This study aimed to develop a CBD-loaded O/A microemulsion (CBD-ME) formulated as microemulgel (CBD-MEgel), suitable for local administration. The developed CBD-ME consisted of Solutol HS 15 (20%, surfactant), Transcutol P (9%, cosolvent), isopropyl myristate (5%, oil phase), water (66%) and 1% w/w CBD. Globules had polydispersity index less than 0.23±0.02 and size of 35±2 nm; these values did not change after loading CBD and gelling the formulation with Sepigel 305 obtaining a clear and homogeneous formulation with a pH of 6.56±0.20, suitable for cutaneous application. Viscosity properties were investigated by the rotational digital viscometer, at both 21±2 °C and 35±2 °C. Viscosities of CBD-MEgel were 439,000±4,243 mPa·s and 391,000±1,414 mPa·s respectively. The release studies displayed that 90±24 μg/cm² of CBD were released in 24 hours. The CBD permeability, evaluated using Franz diffusion cells and rabbit ear skin, was 3±1 μg/cm². Skin-PAMPATM gave a CBD effective permeability of (1.67±0.16) ·10⁻⁷ cm/s and an absorbed dose of 115.30±16.99 µg/cm² after 24h. Lastly, physical and chemical stability of both CBD-ME and CBD-MEgel were evaluated over a period of 3 months, showing optimal shelf-life at the storage conditions.
... According to the USP chapter <1151>, there are four general classes of ointment bases: oleaginous bases, absorption bases, water removal bases and water-soluble bases. These bases are described in more detail in the review article by Garg et al. [96]. In the case of non-aqueous ointments, the nanosuspension is subjected to spray drying or freeze-drying to remove the solvent phase before preparation. ...
Article
The barrier function of skin and the non-optimal physicochemical properties of drugs present challenges to the skin penetration of many drugs, motivating the development of novel drug-delivery systems. Recently, nanocrystal-based formulations have been investigated for topical drug delivery and have demonstrated improved skin penetration. This review highlights barriers in skin penetration, current techniques to improve topical delivery and the application of nanocrystals to conquer obstacles for topical delivery. Nanocrystals can improve delivery through the skin by mechanisms including the creation of a higher concentration gradient across skin resulting in increased passive diffusion, hair follicle targeting, formation of diffusional corona, and adhesion to skin. These mechanisms are of interest for formulation scientists seeking to develop products involving molecules that are ‘difficult-to-deliver’ topically.
... The dehydration effect caused by the vehicle may limit the therapeutic effect and may also induce a chronic inflammatory response [57]. Unlike other delivery vehicles, the ointment base affects the active compound's bioavailability due to its occlusion effect on the stratum corneum, which then increases drug penetration/diffusion across the skin [59]. ...
Article
Full-text available
Skin barrier functions, environmental insults, and genetic backgrounds are intricately linked and form the basis of common inflammatory skin disorders, such as atopic dermatitis, psoriasis, and seborrheic dermatitis, which may seriously affect one’s quality of life. Topical therapy is usually the first line of management. It is believed that successful topical treatment requires pharmaceutical formulation from a sufficient dosage to exert therapeutic effects by penetrating the stratum corneum and then diffusing to the target area. However, many factors can affect this process including the physicochemical properties of the active compound, the composition of the formulation base, and the limitations and conditions of the skin barrier, especially in inflammatory skin. This article briefly reviews the available data on these issues and provides opinions on strategies to develop a suitable formulation for inflammatory skin disease treatment.
... The word topical dosage forms encompass dosage forms applied on the surface of the skin, nail, mucous membranes, and eye. Topical dosage forms are being preferred over other dosage forms as they provide local therapeutic effect when applied on the skin or mucous membranes (1). All these biological barriers are formidable and resist penetration of most of the drug molecules except a few which possess desirable physicochemical characteristics favoring penetration. ...
... Surfactants additionally lessen the interfacial pressure between the stages, working with the development of little drops after blending. 3 Levofloxacin is a broad-spectrum, 3 rd generation fluoroquinolone antibiotic and optically lively L-isomer of ofloxacin with antibacterial activity. Levofloxacin diffuses through the bacterial cell wall and acts by way of inhibiting DNA gyrase (bacterial topoisomerase II), an enzyme required for DNA replication, RNA transcription, and restoration of bacterial DNA. ...
Article
The aim of the current study is to develop Levofloxacin loaded microemulsion formulated with mustard oil for better skin penetration effect and to obtain combined effect of both the oil and the drug to improve the efficacy with a reduced dose. Primarily we developed a pseudo ternary phase diagrams to find out the region of microemulsion formation zone by using oil (mustard oil), surfactant (Tween 20 and Tween 80), and co-surfactant (propylene glycol) by water titration method. We formulated six different formulations (MM1-MM6) by varying the concentrations of the oil water and surfactant and cosurfactant ratio. The developed microemulsion formulation was characterized for various parameters % Transmittance, viscosity, pH, drug content, surface morphology, zeta potential, and in-vitro drug release study. The selected microemulsion formulation is further converted in to microemulgel by dispersing the ME into 2%w/W Carbopol gel (MM-G) and various parameters are evaluated for the gel. The antimicrobial efficacy was carried out for ME and Microemulgel by well diffusion method against Staphylococcus aureus (MTCC: 737) compared with the standard streptomycin which showed that MM3 and MM-G have a better antimicrobial effect than standard proved that the drug levofloxacin and the mustard oil shows the synergistic effect in the Microemulsion formulation with better skin penetration effect.
... In modern medicine, ointments are used in various fields of surgery, ophthalmology, gynecology, combustiology, etc. [3][4][5][6][7][8][9] The packaging of these ointments is also done in solid packaging with unreactive coating promoting the use of ointment compositions as promising for cosmetic purposes, for example, to soften the skin, nourish it with vitamins, trace elements, and treat various cosmetic skin imperfections e.g. freckles, removing age spots, hair, and others [10][11][12][13][14]. Ointments are the optimal dosage form, which consists of a combination of components of different chemical nature, aggregate state, and biological activity [15][16][17][18]. ...
Article
Full-text available
A complex modern study of the ratio effect of components of an ointment composition based on highly dispersed Zinc oxide modified with nanoscale silver on its physical and chemical properties is performed. It was found that at a concentration of glycerol equal to C = 10%, and at a concentration of methylcellulose C = 3%, the value of the active acidity of the ointment composition is optimal (pH = 6.5-7). Studies of the structural and mechanical properties of the ointment composition have shown that the wound-healing ointment composition is elastic and has thixotropy, which makes it possible to use it in the treatment of wound surfaces with complex relief.
... They are relatively simple to prepare and manage though they have a rapid drug release rate. As well as, they are very biocompatible and bio-adhesive, thus simply adhere to the mucosa in the periodontal pocket (5) . Metformin (MF) as an antidiabetic drug can excess the peripheral load of glucose and reducing the production of hepatic glucose (6) . ...
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Background: adjunctive local periodontal therapy is one of the best options to improve the health of the pocket tissue. The comparison of local effects of simvastatin and metformin as aid in enhance the healing of periodontal tissue is the point of importance.
... Phage formulations in the dry state offer more options for delivery routes and dosage forms with higher patient compliance, such as dry powder inhalation (DPI), oral dosage forms, topical pastes and dusting powders [22][23][24]. For instance, phage formulations for pulmonary delivery to treat lung infections have been previously reported, particularly for chronic S. aureus and P. aeruginosa infections associated with cystic fibrosis (CF) [16,20,25]. ...
Preprint
Full-text available
Recently, therapeutic uses of bacteriophage (phage) are gaining increased attention, yet common liquid phage formulations require cold chain storage that limits their potential use. Phage therapy is considered as an alternative to antibiotics for bacterial infections and more significantly a promising solution for the ever-increasing prevalence of multi-drug resistance (MDR) pathogens. One of the most promising applications of this therapy is to treat pulmonary bacterial infections. To efficiently deliver therapeutic phage to the lungs, phage formulations that allow for nebulization or dry powder inhalation are under active development. Several conventional particle engineering technologies have been applied in the development of dry powder inhalers (DPI), including spray drying, spray freeze drying, and atmospheric spray freeze drying, but these processes have their own disadvantages that limit their use with bacteriophage formulations and delivery. In our work, we hypothesize that thin film freeze-drying (TFFD) can be used to produce brittle matrix powders containing phage that may be suitable for delivery by several routes of administration, including by nebulization after reconstitution and by intranasal or inhalation delivery of the resulting dry powder. Here we selected T7 bacteriophage as our model phage in a preliminary screening study and found that a binary excipient matrix of sucrose and leucine at ratios of 80:20 or 75:25 by weight, protected bacteriophage from the stresses encountered during the TFFD process. In addition, we confirm that incorporating a buffer system during the TFFD process significantly improved the survival of phage during the ultra-rapid freezing step of the TFFD process and subsequent sublimation step in the lyophilization process. This preservation of phage bioactivity was significantly better than that observed for formulations without a buffer system. The titer loss of phage in standard SM buffer (Tris/NaCl/MgSO 4 /gelatin) containing formulation was as low as 0.2 log plaque forming units (pfu), which indicates that phage functionality was preserved after the TFFD process. Moreover, the presence of buffers markedly reduced the geometric particle sizes as determined by a dry dispersion method using laser diffraction, which indicates that the TFFD phage powder formulations were easily sheared into smaller powder aggregates, an ideal property for facilitating pulmonary delivery through DPIs. From these findings, we show that TFFD is a particle engineering method that can successfully produce phage containing powders that possess the desired properties for bioactivity and inhalation therapy.
... [1][2][3][4][5][6][7] To improve therapeutic efficiency or pharmacokinetic profiles, drugs administered via the topical route are generally made in a dosage system, such as a patch, gel, lotion, cream, ointment, or spray. [8][9][10] However, the concern is that patch preparations still leave drug residues after use and can be deliberately abused. 11 Patch preparations are also often associated with hypersensitivity, irritation, and blistering. ...
Article
Full-text available
Film-forming sprays offer many advantages compared to conventional topical preparations because they can provide uniform drug distribution and dose, increased bioavailability, lower incidence of irritation, continuous drug release, and accelerated wound healing through moisture control. Film-forming sprays consist of polymers and excipients that improve the characteristics of preparations and enhance the stability of active substances. Each type of polymer and excipient will produce films with different features. Therefore, the various types of polymers and excipients and their evaluation standards need to be examined for the development of a more optimal form of film-forming spray. The selected literature included research on polymers as film-forming matrices and the application of these sprays for medical purposes or for potential medical use. This article discusses the types and concentrations of polymers and excipients, sprayer types, evaluations, and critical parameters in determining the sprayability and film characteristics. The review concludes that both natural and synthetic polymers that have in situ film or viscoelastic properties can be used to optimise topical drug delivery.
... Hence, at high levels of x1, a general trend towards HC retention into more viscous systems is expected, limiting its skin uptake and diffusion. Indeed, viscosity has long been described as an important factor for semisolid formulations as it may influence the release of drug by generally limiting the diffusion rate from the vehicles and, consequently, the drug available for skin permeation [89,90]. Conversely, the acquired results demonstrate that medium levels of x1 are preferred for the achievement of greater penetration results. ...
Article
Full-text available
This work aims at providing the assumptions to assist the sustainable development of cream formulations. Specifically, it envisions to rationalize and predict the effect of formulation and process variability on a 1% hydrocortisone cream quality profile, interplaying microstructure properties with product performance and stability. This tripartite analysis was supported by a Quality by Design approach, considering a three-factor, three-level Box–Behnken design. Critical material attributes and process parameters were identified from a failure mode, effects, and criticality analysis. The impact of glycerol monostearate amount, isopropyl myristate amount, and homogenization rate on relevant quality attributes was estimated crosswise. The significant variability in product droplet size, viscosity, thixotropic behavior, and viscoelastic properties demonstrated a noteworthy influence on hydrocortisone release profile (112±2-196±7 μg/cm2/√h) and permeation behavior (0.16±0.03-0.97±0.08 μg/cm2/h), and on the assay, instability index and creaming rate, with values ranging from 81.9 to 120.5%, 0.031±0.012 to 0.28±0.13 and from 0.009±0.000 to 0.38±0.07 μm/s, respectively. The release patterns were not straightforwardly correlated with the permeation behavior. Monitoring the microstructural parameters, through the balanced adjustment of formulation and process variables, is herein highlighted as the key enabler to predict cream performance and stability. Finally, based on quality targets and response constraints, optimal working conditions were successfully attained through the establishment of a design space.
... In addition to penetration enhancers, several other excipients/additives such as solvents, co-solvents, surfactants, humectants, thickening agents, and others are used in the development of topical/transdermal formulation. These agents act as inactive ingredients and control the extent of absorption (thermodynamic activity and partition coefficient), maintain the viscosity and pH, improve the stability as well as organoleptic properties, and increase the bulk of the formulation [15,16]. Similar to every other dosage form, topical formulation development program also involves pre-formulation development, formulation development, performance (in vitro and in vivo), and stability. ...
Article
Full-text available
Topical drug delivery is an attractive alternative to conventional methods because of advantages such as non-invasive delivery, by-pass of first pass metabolism, and improved patient compliance. However, several factors such as skin, physicochemical properties of the drug, and vehicle characteristics influence the permeation. Within a formulation, critical factors such as concentration of drug, physical state of drug in the formulation, and organoleptic properties affect the flux across the skin. The aim of the study was to develop and investigate topical semisolid preparations (creams and gels) with ibuprofen as the model drug and investigate the effect of various formulation parameters on the in-vitro performance across the Strat-M® membrane using flow-through cells. In addition, the physical stability of the developed formulations was investigated by studying viscosity, pH, and appearance. All the formulations developed in the study had appealing appearance with smooth texture and no signs of separation. Viscosity and pH of the formulations were acceptable. Cumulative amount of drug permeated at the end of 24 h was highest for clear gel (3% w/w ibuprofen; F6: 739.6 ± 36.1 µg/cm2) followed by cream with high concentration of ibuprofen in suspended form (5% w/w; F3: 320.8 ± 17.53 µg/cm2), emulgel (3% w/w ibuprofen; F5: 178.5 ± 34.5 µg/cm2), and cream with solubilized ibuprofen (3% w/w; F2A: 163.2 ± 9.36 µg/cm2). Results from this study showed that permeation of ibuprofen was significantly influenced by formulation parameters such as concentration of ibuprofen (3% vs. 5% w/w), physical state of ibuprofen (solubilized vs. suspended), formulation type (cream vs. gel), mucoadhesive agents, and viscosity (high vs. low). Thus, findings from this study indicate that pharmaceutical formulation scientists should explore these critical factors during the early development of any new topical drug product in order to meet pre-determined quality target product profile.
... Conventional topical dosage form for psoriasis treatment such as ointment, creams, gels have poor penetration power to the skin and patient discomfort due to stickiness and greasiness [8]. Lipid based nano-vesicles such as niosomes, ethosomes, transferosmes have been shown to provide a more useful drug carrier for antipsoriatic therapy with excellent penetration to skin, patient compliance and improved bioavailability [9][10]. ...
Article
The present work was aimed to develop a transferosomal gel of ibuprofen (IBU) for the amelioration of psoriasis like inflammation. Three formulation of IBU loaded transferosomes (TFs1-TFs3) were prepared using different proportions of lipid (phospholipon 90H) and surfactant (tween 80) and further evaluated for vesicle size, zeta potential (ZP), entrapment efficiency and in vitro drug release. The IBU loaded transferosomes (TFs2) was optimized with vesicle size (217±8.4 nm), PDI (0.102), ZP (-31.5±4.3 mV), entrapment efficiency (88.4±6.9%) and drug loading (44.2±2.9%). Further, the optimized IBU loaded transferosomes (TFs2) was incorporated into 1% carbopol 934 gel base and characterized for homogeneity, extrudability, viscosity and drug content. The in vivo pharmacodynamic study of gel exhibited reduction in psoriasis like inflammation in mice. The ibuprofen loaded transferosomal gel was successfully developed and has shown the potential to be a new therapy against psoriasis like inflammation.
... [1] Topical dosage form includes creams, ointments, gel, solution, lotion, and spray. [2] Creams are mostly emulsion-based products which are either water in oil or oil in water type. Emulsions are a mixture of the oil phase and water phase stabilized by surfactant(s). ...
Article
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The dissolution of the drug in the vaginal cavity strongly influences the efficacy of the product due to insufficient moisture at the vaginal site. This study was undertaken to develop semi-solid dosage forms of miconazole nitrate to optimize its release. Formulations containing miconazole nitrate at 2% were developed using hypromellose gel, non-ionic emulsion, and cationic emulsion. The effect of penetration enhancers such as propylene glycol, dimethyl sulfoxide (DMSO), and diethylene glycol monoethyl ether at various concentrations was studied. Diffusion studies were carried out to evaluate the drug release and compared it against a commercial product. Formulation with the highest drug release was further evaluated at half (1%) drug concentration. Formulation with reduced drug levels along with the commercial product was evaluated for drug release for an extended time using human cadaver skin. The general order of average cumulative drug release from three bases was observed to be cationic emulsion> hydroxypropyl methylcellulose> non-ionic emulsion. Among all samples, the cationic emulsion with 5% DMSO gave a maximum drug release of 7.27±0.2 mg/cm2 with a flux of 0.70 mg/cm2/min compared to only 3.09±0.1 mg/cm2 drug release with 0.51 mg/cm2/min flux for brand product. The average cumulative drug release for formulation with half (1%) drug and brand (2% drug) over a period of 12 h through human cadaver skin was observed to be 8.28±0.9 mg/cm2 and 8.71±0.9 mg/cm2, respectively. This observation was in conformance with the in vitro antifungal studies showing an equivalent zone of inhibition
... [27,28] Also, it has a strong antimicrobial activity which makes it suitable for preventing the growth of both Gramnegative S. aureus and S. Typhimurium [29] on the wound area. [27,30,31] Moreover, the CmZnO-NP is considered as the enriched source of Zinc ions, which can be efficiently delivered by target cells. Regarding the important role of zinc ions in gene transcription, mRNA translation, and cell proliferation, it is considered as one of the main requirements for improving a facilitating the wound healing process. ...
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Curcumin and Zinc oxide nanoparticle (ZnO-NP) are known as organic and mineral wound healing agents, respectively. In this study, we aimed to green-synthesize the curcumin-mediated ZnO-NP (CmZnO-NP) and evaluate biological properties. In this study, CmZnO-NP were synthesized and after characterizing (DLS, XRD, FT IR, FESEM) its antioxidant effects (ABTS, DPP H), toxicity (MTT) and wound healing (H&E staining and gene expression) were investigated. The 30.77-nm CmZnO-NP significantly scavenged both free radicals. Also, its wound healing activity was observed by detecting the meaningful reduction in the length and depth of the rat’s skin wound. The collagen and VEGF up-regulation of the rat skin tissue following the increasing CmZnO-NP treatment doses confirmed its wound healing potential. Due to antioxidant and improved wound healing activities of the CmZnO-NP, it has the potential to be studied as an efficient wound healing compound.
... Tapioca starch is particularly useful as it gives a very smooth feel to the product. Due to the chemically inert nature of talc and kaolin, they are the most commonly used ingredients in the formulation of dusting powder [104]. The presence of powders formed by spherical particles in formula allows an excellent spreadability increasing the duration and decreasing the transferability of the make-up. ...
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The face powder was demanded by many nations in the world in the beginning AD and in Asia white skin was believed to be the sign of aristocratism, membership of the elite, and yet, white color is the pure symbol of the internal beauty and nobility. In addition, some face powders are sold in varying specialty shades to suit different skin needs; for example, a face powder with a greenish tinge will minimize the appearance of redness, while a purple-tinted powder may help the appearance of sallow or yellow skin. There is a legitimate reason to use face powder, and the pharmacopeias prescribe them in the treatment of many skin affections. At all events the proper use of powder is beneficial, it lightly covers and unifies a complexion, hiding the ravages of time, improving even the beautiful face. Face powder comes in different shades to match varying skin tones, and it is a good idea to choose the skin tone that most closely matches the natural skin. This will help the makeup appear more natural; it should be virtually unnoticeable. It may be necessary to use different face powders for summer and winter, as the skin may become tanner in the summer, or drier and in need of extra moisture in the winter. They are of benefit in acne, freckles, sunburn and red nose. Beneath their attractive aspect and odor, face powders should be made by the perfumer to combine the qualities of an elegant cosmetic and therapeutic agent; they must primarily possess adherence, lightness and be transparent; secondly, they should be detergent and delicately absorbent in order to aid the natural functions of the skin, taking up the fatty matters not easily dislodged by water; they should also tend to increase the natural elasticity and regular functions of the skin.
... Biliary salts were found to be less irritating, to have lower hemolytic activity and less protein release than other surfactants [40]. Gelling agents are used [41], since increasing solution viscosity may prolong the therapeutic effect of nasal preparations. However, increase the viscosity retards diffusion of drug from the matrix and may cause unwanted delay in drug absorption [42]. ...
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Drug delivery by the intranasal route allows both systemic absorption and non-invasive brain targeting, due to the unique connection provided by the olfactory and trigeminal nerves between the brain and the external environment. Lipid nanocarriers can improve intranasal drug delivery by enhancing bioadhesion to nasal mucosa, and by protecting the encapsulated drug from biological degradation and transport efflux proteins. In this study two different biocompatible lipid nanocarriers were compared: nanoemulsions and solid lipid nanoparticles. The nasal uptake was investigated by labeling the nanocarriers lipid matrix with two fluorescent probes, 6-coumarin and rhodamine B, both lipophilic, yet characterized by different water solubility, in order to mimic the behavior of hypothetic drug compounds. Ex vivo permeation, in vivo pharmacokinetics and biodistribution studies were performed. 6-coumarin, water insoluble and therefore integral with the lipid matrix, was taken up to a limited extent, within a long timeframe, but with a proportionally more pronounced brain accumulation. In nanoemulsions soluble rhodamine B showed a relevant systemic uptake, with good bioavailability, likely due to the prompt release of the probe at the nasal mucosa.
... In light, developing topical platforms present attractive therapeutic aspects in terms of lower harm or incidence of serious adverse effects of systemically administered antifungal medications (oral or injectable), better efficacy and the ability to simply terminate the medication when necessary, hence, greater patient compliance (Estrada, 1987;Rezabek & Friedman, 1992). Indeed, effectiveness of any topically applied antifungal agent mainly depends on its concentration in the infected area, its activity spectrum and safety (Kalavathy et al., 2005;Garg et al., 2015). ...
... Skin being the largest organ and the outermost layer of the human body is very much suited to targeted delivery of therapeutic agents through topical delivery [76]. This is because the human skin suffers from common diseases such as acne, wound, and other skin disorders [77]. The correct combination of active ingredients and base components would allow for a wide range of topical preparations suitable for delivering the active ingredients [76]. ...
... An ideal gel preparation should be sufficiently mobile in order to facilitate delivery of the dosage form to the application site yet adequately viscous to remain at the application site at an effective concentration [63,64]. The gel preparations in this work exhibited adequate viscosity ranging from 3355.00 ± 13.22 to 4519.67 ± 40.10 cP (i.e., within the typical viscosity range of~1000 cP to~100,000 cP when the gelling agents are used in a concentration of less than 10% [65]. ...
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With the rising public awareness of environmental issues, consumers are increasingly demanding skin care products that create less environmental impact but still provide the same or even greater efficacy. In the skin care arena, microemulsions have been receiving increased attention as the promising delivery technology of skin care actives. Essential oils such as peppermint oil, lavender oil and eucalyptus oil are purported to have excellent antioxidant and antimicrobial properties that could be used as the eco-friendly alternatives for synthetic antioxidants and preservatives in the skin care formulations. This work therefore seeks to develop eco-friendly skin care formulations based on microemulsions of essential oil. Peppermint oil, lavender oil and eucalyptus oil were used as the oil phase to formulate naringin-loaded microemulsions, which demonstrated similar or better antioxidant and antimicrobial properties compared to the synthetic ones. When formulated into gel form, naringin-loaded microemulsion-gel formulations showed enhanced stability and release profile over their unformulated counterpart. Hence, microemulsions of essential oil developed in this work conferred a 4-fold benefits to the skin care formulations: (1) improved release (membrane permeation) of skin care active, (2) improved stability of skin care active, (3) as an eco-friendly alternative to synthetic antioxidant, and (4) a self-preserving system.
... To design the topical formulation, various delivery systems such as patches, pastes, creams, and ointments have been used (Garg et al., 2015). However, these all systems have several limitations. ...
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To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM–TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM–TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM–TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM–TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM–TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM–TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.
... Also, AuNPs provide antimicrobial action via ROS-independent pathways thereby stimulating angiogenesis and wound healing [174,175]. Likewise, ZnO NPs are antibacterial, anti-inflammatory, and antiseptic, and are frequently employed in the manufacture of skin creams, and ointments [176]. Due to their tiny size and high surface-to-volume ratio, ZnO exhibits greater Dendrimers Anti-inflammatory, increased production of transforming growth factor (TGF)-b1, interleukin (IL)-4 and IL-10, induced fibroblast proliferation, and gene therapy ...
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Chronic wounds have been a global health threat over the past few decades, requiring urgent medical and research attention. The factors delaying the wound-healing process include obesity, stress, microbial infection, aging, edema, inadequate nutrition, poor oxygenation, diabetes, and implant complications. Biomaterials are being developed and fabricated to accelerate the healing of chronic wounds, including hydrogels, nanofibrous, composite, foam, spongy, bilayered, and trilayered scaffolds. Some recent advances in biomaterials development for healing both chronic and acute wounds are extensively compiled here. In addition, various properties of biomaterials for wound-healing applications and how they affect their performance are reviewed. Based on the recent literature, trilayered constructs appear to be a convincing candidate for the healing of chronic wounds and complete skin regeneration because they mimic the full thickness of skin: epidermis, dermis, and the hypodermis. This type of scaffold provides a dense superficial layer, a bioactive middle layer, and a porous lower layer to aid the wound-healing process. The hydrophilicity of scaffolds aids cell attachment, cell proliferation, and protein adhesion. Other scaffold characteristics such as porosity, biodegradability, mechanical properties, and gas permeability help with cell accommodation, proliferation, migration, differentiation, and the release of bioactive factors.
... Focusing on the viscosity value of the hydrogels, which is a critical quality attribute, we can observe that all of them present a value coherent with the appropriate consistency for topical application, and in line with viscosities reported in the literature for topical formulation products [55]. ...
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Topical delivery has received great attention due to its localized drug delivery, its patient compliance, and its low risk for side effects. Recent developments have focused on studying new drug delivery systems as a strategy for addressing the challenges of current topical treatments. Here we describe the advances on an innovative drug delivery platform called DELOS nanovesicles for topical drug delivery. Previously, the production of DELOS nanovesicles demonstrated potentiality for the topical treatment of complex wounds, achieving well-tolerated liquid dispersions by this route. Here, research efforts have been focused on designing these nanocarriers with the best skin tolerability to be applied even to damaged skin, and on exploring the feasibility of adapting the colloidal dispersions to a more suitable dosage form for topical application. Accordingly, these drug delivery systems have been efficiently evolved to a hydrogel using MethocelTM K4M, presenting proper stability and rheological properties. Further, the integrity of these nanocarriers when being gellified has been confirmed by cryo-transmission electron microscopy and by Förster resonance energy transfer analysis with fluorescent-labeled DELOS nanovesicles, which is a crucial characterization not widely reported in the literature. Additionally, in vitro experiments have shown that recombinant human Epidermal Growth Factor (rhEGF) protein integrated into gellified DELOS nanovesicles exhibits an enhanced bioactivity compared to the liquid form. Therefore, these studies suggest that such a drug delivery system is maintained unaltered when hydrogellified, becoming the DELOS nanovesicles-based hydrogels, an advanced formulation for topical use.
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ABSTRAK Akar kuning (Arcangelisia flava Merr.) merupakan salah satu tanaman yang tumbuh di Kalimantan Tengah dan secara turun temurun digunakan sebagai pilihan pengobatan beberapa penyakit kulit dan terbukti mempunyai aktivitas antibakteri. Pembuatan sediaan topikal antibakteri berbahan fraksi aktif A. flava sangat potensial dilakukan untuk mengoptimalkan penggunaan dalam pengobatan sekaligus meningkatkan nilai ekonomis dari A. flava. Tujuan penelitian ini untuk mendapatkan formula gel fraksi aktif A. flava sebagai antibakteri yang paling baik secara fisik.Formula gel dibuat dengan variasi jenis dan konsentrasi gelling agent.Gel fraksi aktif A. flava diuji secara fisika, kimia, dan biologi seperti organoleptis, homogenitas, daya sebar, pH, daya lekat, dan daya hambat terhadap Staphylococcus aureus. Hasil formulasi sediaan gel fraksi aktif A. flava dengan basis NaCMC memenuhi syarat sifat fisik dan zona hambatan 11,6 mm pada Formula 1 dan 13,4 mm pada Formula 2, sedangkan sediaan gel dengan basis Carbophol 943 pada Formula 1 dan 2 memenuhi syarat sifat fisik dan zona hambat 10,9 mm pada Formula 2.Formula gel yang memenuhi kriteria secara fisik adalah Formula 2 dengan Carbophol 1,5% sebagai gelling agent. Kata Kunci: Akar kuning, antibakteri, gel, Staphylococcus aureus ABSTRACT Akar kuning (Arcangelisia flava Merr.) is a plant that grows in Central Kalimantan and has been used as a treatment option for several skin diseases and has been shown to have antibacterial activity. The making of topical antibacterial preparations made from the active fraction of A. flava is very potential to be done to optimize the use in treatment while increasing the economic value of A. flava. The purpose of this study was to obtain the active A. flava fraction gel formula as the best natural antibacterial. The gel formula was made with variations in the type and concentration of the gelling agent. Arcangelisia flava Merr. active fraction gel was tested physical, chemical, and biological, such as organoleptic, homogeneity, spreadability, pH, adhesion, and bacterial inhibitionagainst Staphylococcus aureus. The results of the formulation of the active gel of A. flava based on NaCMC base fulfills physical condition requirements and shows an inhibition zone of 11.6 mmin Formula 1 and 13.4 mm in Formula 2, while gel preparation based on Carbophol 943 Formula 1 and 2 fulfill the physical characteristic requirements and show the inhibition zone of 10.9 mm in Formula 2.Gel formula that meets the physical criteria is Formula 2, with 1.5% Carbophol as a gelling agent. Keywords: Akar kuning, antibacterial, gel, Staphylococcus aureus
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The management of nail psoriasis is an arduous task owing to the disease manifestations and anatomical structure of the nail plate. Although various treatment therapies are available for nail psoriasis, topical therapy is contemplated as one of the most favorable options as systemic therapies are accompanied by numerous side effects that result in patient incompliance. The topical formulations including creams, gels, ointments, and nail lacquers have been used as delivery systems for various antipsoriatic drugs. Among these, nail lacquers emerge to be promising and patient friendly formulations. However, the major defiance with topical delivery is inefficacious penetration of drug through impenetrable keratinized nail plate to reach the target sites: nail matrix and nail bed. Therefore, in order to obtain effectual drug delivery systems that can retain/remain on the nail plate for a prolonged period of time and deliver the drug across it, systematic approaches like quality by design (QbD) need to be followed so that the desired quality can be “built in” the system rather than to rely solely on retrograde evaluation. Furthermore, more advances in research are still required to develop a validated animal model so as to determine the efficacy of the formulation and to establish a mathematical model that can help in predicting the desirable attributes of the formulation and permeation of various molecules through the nail plate.
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Topical treatments have been widely adopted to address a broad range of conditions across multiple sites thanks to their convenience, versatility, and effectiveness. While bypassing systemic biobarriers and avoiding systemic side effects by delivering directly to the target tissue, topical treatments still face significant local biobarriers that limit their efficacy. The toolset available for nanodelivery systems and their inherent multifunctionality can contribute to simultaneously address otherwise intractable challenges related to barrier function evasion, drug solubility, bioavailability, pharmacokinetics, smart and sustained release, quantitative co-delivery, and local targeting which are key to successful topical treatments. This review summarizes the outstanding challenges associated with the topical treatments of key diseases of the skin, mucosae, eyes, and ears, and highlights how nanodelivery systems are being developed to address them effectively.
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Phage therapy has gained prominence due to the increasing pathogenicity of “super bugs” and the rise of their multidrug resistance to conventional antibiotics. Dry state formulation of therapeutic phage is attractive to improve their “druggability” by increasing their shelf life, improving their ease of handling, and ultimately retaining their long-term potency. The use and selection of excipients are critical to stabilize phage in solid formulations and protect their viability from stresses encountered during the solidification process and long-term storage prior to use. Here, this review focuses on the current classes of excipients used to manufacture dry state phage formulations and their ability to stabilize and protect phage throughout the process, as discussed in the literature. We provide perspective of outstanding challenges involved in the formulation of dry state phage. We suggest strategies to improve excipient identification and selection, optimize the potential excipient combinations to improve phage viability during formulation, and evaluate new methodologies that can provide greater insight into phage-excipient interactions to improve design criteria to improve formulation of dry state phage therapeutics. Addressing these challenges opens up new opportunities to re-design and re-imagine phage formulations for improved efficacy as a pharmaceutical product.
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Chapter
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The Federal Food Drug, and Cosmetic Act 2018 clearly defines the terms “drugs” and “cosmetics”. Surprisingly, “cosmeceuticals” do not find any mention under this Act. The cosmetic industry commonly uses this word to refer cosmetic products that have medicinal or drug-like benefits. Cosmeceuticals are the fastest growing segment of the personal care industry. A new generation of cosmeceuticals containing more efficacious and stable active ingredients incorporated into versatile nanocarriers like liposomes, nanoparticles, buckyballs, nanoemulsions, dendrimers, fullerenes, microgels, nanogels, nanocrystals, nanogold and nanosilver have come into existence. They have been termed as “nanocosmeceuticals”. A wide range of nanocosmeceuticals are presently available as antiaging products, skin cleansers, moisturisers and haircare products as colour cosmetics. There are more than 20 nanocosmeceutical based products commercially available and hundreds of patents pertaining to nanocosmeceuticals. Nanocosmeceuticals exhibit improved activity because of better entrapment efficiency, enhanced skin penetration, and retention leading to prolonged release of active ingredients. In spite of their fascinating and innumerable advantages, they have lot of safety concerns which should never be overlooked. There are reports suggesting damage to body tissues, denaturation of proteins, alteration in genetic material, abnormal immune system reactions and increased oxidative stress. Threats to the marine life and soil have also been reported due to their casual disposals to streams, oceans and seas. However if used cautiously this advanced miniaturization technology has the potential to bring significant advances in the cosmetic industry. It is foreseen that, in the coming years, the market will be captured exclusively by nanocosmeceuticals.
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In this study, a stable and highly skin-permeable topical delivery system for itraconazole (ITZ) was designed to provide effective treatment against superficial mycosis. Herein, ITZ was incorporated into a solution composed of ethanol, benzyl alcohol, hydrochloric acid, Transcutol P, and cyclomethicone as a delivery vehicle, solubilizer, protonating agent, permeation enhancer, and spreading agent, respectively. At 72 h, the optimal topical ITZ formulation (ITZ–TF#11) exhibited 135% enhanced skin permeability, which led to increases in drug deposition in the stratum corneum, epidermis, and dermis of 479%, 739%, and 2024%, respectively, compared with the deposition of 1% ITZ in ethanol (control). Moreover, on day 7, ITZ–TF#11 demonstrated 2.09- and 2.30-fold enhanced nail flux and drug deposition, compared with the control. At a dose of 40 mg/kg/day, ITZ–TF#11 showed 323% greater lesion recovery, a 165% lower mean erythema severity score, and a 37% lower mean logarithm of viable fungal cells in skin in the treated area, compared with mice that received oral ITZ at the same dose. Overall, the findings imply that ITZ–TF#11 is a superior alternative to oral ITZ for treatment of superficial mycosis.
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Objective Topical application of ambonese banana (Musa paradisiaca var. sapientum (L.) kuntze) stem sap gel (GEGPA) on the socket wound area showed an increase in the expression of platelet-derived growth factor-BB, while decrease in the expression of matrix metalloproteinase-2 and 9. The aim of this study is to achieve standard formulation of GEGPA through stability, viscosity, distribution area, and drugs release for oral gel wound healing. Materials and Methods This is an in vitro and in vivo study with the randomized posttest only control group design. The gel was formulated according to the composition of each group by adding hydroxypropyl methylcellulose (HPMC), Lexgard, propylene glycol, and cold water to obtain 100 g of gel. Observations were made through the following tests: stability, viscosity, distribution area, drug release, and histopathological analysis of tooth extraction wound healing. Statistical analysis Data were analyzed using a one-way analysis of variance (α = 0.05) with GraphPad Prism-8 statistical software. Results The study showed that the GEGPA formulation was stable against changes in consistency, color, smell, homogeneity, and pH value. There is a significant difference between groups with respect to viscosity (p = 0.0001), adhesion (p = 0.004), dispersion (p = 0.000), and fibroblast cell numbers on days 3 and 5 (p = 0.007 and p = 0.001). There is no interaction between the active ingredients and the gel base of all formulations. Formulation 3 had better properties in terms of viscosity, broad distribution, and drug release compared with other groups. Application of GEGPA to tooth extraction wounds showed a significant proliferation of fibroblast cells on days 3 and 5. Conclusions The formulation of M. paradisiaca var. sapientum (L.) kuntze extract with HPMC and propylene glycol obtained a gel preparation, GEGPA, that was organoleptically stable and met the topical gel standard for wounds in the oral cavity.
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The paper is a compilation of varied excipients currently employed in the manufacturing of different dosage forms. Advancements in drug delivery can be accomplished only with accomplishments in excipient industry by way of isolating, extracting or synthesizing newer excipients of plant and/or synthetic origin with biodegradable and/or biocompatible properties, designing tailor made excipients for specific dosage forms either in the cosmeceutical, nutraceutical or drug delivery systems for varied routes of administration embedded with QbDparadigmns, or envisioned newer techniques viz., the principles of green chemistry. Despite such remarkable achievements in the excipient industry, drug interactions, packaging incompatabilities are inevitable. The future of this industry is poignantly decisive on striking a chord between the two. An excipient is stated to be defined by Beena P et al as"A substance formulated alongside the active ingredient of a medication, included for long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (that are often referred to as bulking agents, fillers, or diluents), or to grant a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility" 1. Another definition stated excipients to be "A pharmacologically dynamic medication or pro-drug which are incorporate into the assembling procedure or are contained in a completed pharmaceutical item measurements form" 2. Many excipients have envisaged numerous applications in the pharmaceutical industry, especially in the manufacturing process where its appropriate selection is brusquely governed by a myriad of factors-the routes of administration, the nature and type of dosage forms and the delivery systems, the physio-chemical properties of the active ingredients, etc. that inadvertently converged onto a "structure-property-application" paradigm.
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Creams are a type of pharmaceutical product used for daily skin care, as well as medicated and non-medicated applications. It is also regarded as a vital component of cosmetics. When the dosage form is creams, the route of delivery is the skin. The rate of medication absorption and penetration is influenced by a variety of factors in the skin. The topical medication delivery system is a method of delivering drugs to the skin. Topical medication administration has the advantage of bypassing first-pass metabolism, hydrating the skin, and providing emollient qualities. Creams are viscous or semisolid emulsions that come in O/W or W/O dosage forms and have a viscosity that changes depending on the quantities of oil and water in them. In terms of functions and qualities, there is a vast range of creams available. Pharmaceutical creams are used for a range of purposes, including cleansing, beautifying, hydrating, and protecting against bacteria and fungi, as well as treating skin wounds. Water, fats, waxes, emollients, colors, scents, and other common ingredients are employed in the creation of practically every cream, resulting in a standard formulation. There are various evaluation parameters available for creams which help the product to match its standard quality eg. pH, viscosity, stability, spreadability, etc.
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The choice of an optimum constructional material for the electrosurgical cutting tools based on nanostructured crystals of partially stabilized zirconia (NPSZe) is substantiated on the basis of criteria of operational stability and functional efficiency. The results of research into adsorption of organic molecules on the surface of the material are used to study the adhesion characteristics of NPSZe. The models of the innovative tools, such as curved bipolar electrosurgical scissors, bipolar forceps, tweezers, and dissectors with nonstick spray, are presented. An experimental model of a high-frequency generator necessary for optimal tool operation is considered.
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Psoriasis is an autoimmune, chronic, inflammatory skin disease characterized by epidermal hyperplasia, proliferation of blood vessels, and infiltration of leukocytes in dermis and epidermis. Several immunosuppressants such as methotrexate (MXT) and cyclosporine are used but they are associated with adverse effects due to down regulation of immune system. Numerous approaches have been explored to overcome the problems of conventional topical system such as high frequency of application, impermeability to skin barrier, and limited efficacy. Photodynamic therapy is another non-invasive technique currently used for skin diseases. The combination of two drugs is also commonly observed to achieve more effective therapy. In the present study, antipsoriatic activity of niosomal formulations for the treatment of psoriasis in combination with narrow and broad band UV radiation had been explored in experimental animal model.
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Topical preexposure prophylaxis interrupts HIV transmission at the site of mucosal exposure. Intermittently dosed vaginal gels containing the HIV-1 reverse transcriptase inhibitor tenofovir protected pigtailed macaques depending on the timing of viral challenge relative to gel application. However, modest or no protection was observed in clinical trials. Intravaginal rings (IVRs) may improve efficacy by providing long-term sustained drug delivery leading to constant mucosal antiretroviral concentrations and enhancing adherence. Although a few IVRs have entered the clinical pipeline, 100% efficacy in a repeated macaque vaginal challenge model has not been achieved. Here we describe a reservoir IVR technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate (TDF) continuously over 28 d. With four monthly ring changes in this repeated challenge model, TDF IVRs generated reproducible and protective drug levels. All TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of four exposures assuming an eclipse of 7 d from infection to virus RNA detection. Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 × 10(5) ng/mL (range 1.1 × 10(4) to 6.6 × 10(5) ng/mL)] and ex vivo antiviral activity of cervicovaginal lavage samples. These observations support further advancement of TDF IVRs as well as the concept that extended duration drug delivery devices delivering topical antiretrovirals could be effective tools in preventing the sexual transmission of HIV in humans.
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Background: Trials of a vaginal Tenofovir gel for pre-exposure prophylaxis (PrEP) for HIV have given conflicting results. Knowledge of concentrations of Tenofovir and its active form Tenofovir diphosphate, at putative sites of anti-HIV functioning, is central to understanding trial outcomes and design of products and dosage regimens. Topical Tenofovir delivery to the vaginal environment is complex, multivariate and non-linear; determinants relate to drug, vehicle, dosage regimen, and environment. Experimental PK methods cannot yield mechanistic understanding of this process, and have uncontrolled variability in drug sampling. Mechanistic modeling of the process could help delineate its determinants, and be a tool in design and interpretation of products and trials. Methods and findings: We created a four-compartment mass transport model for Tenofovir delivery by a gel: gel, epithelium, stroma, blood. Transport was diffusion-driven in vaginal compartments; blood concentration was time-varying but homogeneous. Parameters for the model derived from in vitro and in vivo PK data, to which model predictions gave good agreement. Steep concentration gradients occurred in stroma ≤ 8 hours after gel release. Increasing epithelial thickness delayed initial TFV delivery to stroma and its decline: tmax increased but AUC at 24 hours was not significantly altered. At 24 and 48 hours, stromal concentrations were 6.3% and 0.2% of C(max). Concentrations in simulated biopsies overestimated stromal concentrations, as much as ∼5X, depending upon time of sampling, biopsy thickness and epithelial thickness. Conclusions: There was reasonably good agreement of model predictions with clinical PK data. Conversion of TFV to TFV-DP was not included, but PK data suggest a linear relationship between them. Thus contrasts predicted by this model can inform design of gels and dosage regimens in clinical trials, and interpretation of PK data. This mass transport based approach can be extended to TFV conversion to TFV-DP, and to other drugs and dosage forms.
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Iontophoresis was used to enhance the delivery of aceclofenac (ACF) from topical gels formulated with various polymers for the purpose of relieving pain and inflammation. Gels were formulated from hydroxypropyl methyl cellulose (HPMC), carbopol 934P, and sodium carboxymethyl cellulose (NaCMC). The formulations were evaluated for cathodal iontophoretic delivery of ACF through excised rat abdominal skin at three levels of current density of 0.5, 0.6 and 0.7 mA/cm(2). The in vivo effectiveness of the drug delivered passively as well as under the influence of iontophoresis at pH 7.4 at a current density of 0.5 mA/cm(2) was also investigated using male Albino rats with carrageenan induced paw edema. In the ex vivo studies, though it was clear that iontophoresis significantly increased drug permeation through the excised skin from all formulations; the percentage drug permeated from HPMC gels was superior to that from carbopol 934P or NaCMC gels but increased with an increase in the current density only for the former. The steady state flux, permeability coefficient, enhancement factor were significantly greater from HPMC gels than from the gels of the ionic polymers due to the interference of competitive ions. With iontophoresis, the carrageenan induced paw edema was significantly reduced by 61.53% (P < 0.01) for HPMC gels as compared to the control although passive permeation without iontophoresis showed a 54.6% reduction (P < 0.05) at the end of 4 h. The results of the study indicate that ACF could be administered topically by using iontophoresis from a suitably formulated gel for effective control of pain and inflammation.
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Cetirizine is a piperazine-derived second-generation antihistaminic drug recommended for treatment of pruritus associated with atopic dermatitis. The present investigation encompasses development of a nanosized novel elastic vesicle-based topical formulation of cetirizine dihydrochloride using combination of Phospholipon® 90G and edge activators with an aim to have targeted peripheral H1 antihistaminic activity. The formulation was optimized with respect to phospholipid/drug/charge inducer ratio along with type and concentration of edge activator. The optimized formulation was found to be satisfactory with respect to stability, drug content, entrapment efficiency, pH, viscosity, vesicular size, spreadability, and morphological characteristics. The ex vivo permeation studies through mice skin were performed using Franz diffusion cell assembly. It was found that the mean cumulative percentage amount permeated in 8 h was almost twice (60.001 ± 0.332) as compared to conventional cream (33.268 ± 0.795) and aqueous solution of drug (32.616 ± 0.969), suggesting better penetration and permeation of cetirizine from the novel vesicular delivery system. Further, therapeutic efficacy of optimized formulation was assessed against oxazolone-induced atopic dermatitis in mice. It was observed that the developed formulation was highly efficacious in reducing the itching score (4.75 itches per 20 min) compared to conventional cream (9.75 itches per 20 min) with profound reduction in dermal eosinophil count and erythema score. To conclude, a novel vesicular, dermally safe, and nontoxic topical formulation of cetirizine was successfully developed and may be used to treat atopic dermatitis after clinical investigation.
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Abstract Dermatological inflammatory diseases often affect the scalp and the eyebrows. Common dosage forms available on the market for those situations are lotions; however, the presence of hair limits their use. Gels, for their consistency and adhesiveness, are a suitable alternative to the lotions in these situations. The aim of this study was to develop a new stable gel containing mometasone furoate (MF), with anti-inflammatory activity and a controlled delivery, to improve topical treatment of scalp dermatitis. Pharmaceutical development, physical and chemical characterization, stability, in vitro release and permeation studies and in vivo anti-inflammatory activity were performed. The gel presented an acidic pH and an apparent viscosity of 35 Pa.s. The microbiological analysis showed that the results were within the established specification limits. The release and the permeation profiles suggest that the drug is mainly retained in the upper skin layers. MF gel was tested in an animal model of cutaneous inflammation and presented similar anti-inflammatory activity compared to a commercially available MF dosage form. The gel was chemically, physically and microbiologically stable. The results suggest that the developed hydrogel formulation containing MF can be of actual value for improving the clinical effectiveness in the treatment of scalp dermatitis.
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The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.
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Epithelial tissue provides the body with its first layer of protection against harmful environmental stimuli by enacting the regulatory interplay between a physical barrier preventing the influx of external stimuli and an inflammatory response to the infiltrating stimuli. Importantly, this interdependent regulation occurs on different time scales: the tissue-level barrier permeability is regulated over the course of hours, whereas the cellular-level enzymatic reactions leading to inflammation take place within minutes. This multi-scale regulation is key to the epithelium's function and its dysfunction leads to various diseases. This paper presents a mathematical model of regulatory mechanisms in the epidermal epithelium that includes processes on two different time scales at the cellular and tissue levels. We use this model to investigate the essential regulatory interactions between epidermal barrier integrity and skin inflammation and how their dysfunction leads to atopic dermatitis (AD). Our model exhibits a structure of dual (positive and negative) control at both cellular and tissue levels. We also determined how the variation induced by well-known risk factors for AD can break the balance of the dual control. Our model analysis based on time-scale separation suggests that each risk factor leads to qualitatively different dynamic behaviours of different severity for AD, and that the coincidence of multiple risk factors dramatically increases the fragility of the epithelium's function. The proposed mathematical framework should also be applicable to other inflammatory diseases that have similar time-scale separation and control architectures.
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A hypersensitivity reaction, either anaphylactic or anaphylactoid, is a well-known adverse effect following intravenous and oral administration of vancomycin. The authors report a case of circulatory collapse and its management after the topical application of vancomycin powder during spinal instrumentation surgery. A 52-year-old woman with breast cancer and metastasis to her spine underwent a vertebrectomy of the T-10 vertebra with instrumented reconstruction from T-8 to T-12. The patient was hemodynamically stable during most of the procedure despite a 2-L blood loss requiring administration of crystalloids, colloids, packed red blood cells, and fresh-frozen plasma. During closure of the subcutaneous layer, there was a sudden drop in blood pressure from 120/60 to 30/15 mm Hg and an increase in heart rate from 95 to 105 bpm. No skin erythema or rash was visible, and there was no bronchospasm or increase in airway pressure. The patient was treated with fluids, boluses of ephedrine, phenylephrine, and adrenaline. The operation was completed and the patient woke up neurologically intact but did require blood pressure support with a norepinephrine infusion for the next 4 hours. She was discharged from hospital in a good clinical state on the 4th postoperative day. It was speculated that the rapid absorption of vancomycin powder applied on the surgical wound caused an anaphylactoid reaction and the circulatory collapse. With an increase in the use of topical vancomycin in surgical wounds, communication and awareness among all intraoperative team members is important for rapid diagnosis of an adverse reaction and for appropriate management.
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Date syrup as a nutritional additive and safe alternative to added sugar is one of the best choices for milk flavoring. In this study, a flavored milk beverage was formulated using date syrup for flavoring the product and gum tragacanth to obtain an acceptable mouth feel. Steady shear and dynamic oscillatory rheological properties of the samples contained 3 concentrations (0, 0.1, 0.2, and 0.3%, wt/wt) of 2 types of gum tragacanth (Astragalus gossypinus andAstragalus rahensis) which at 3°C, were studied. Particle size distribution and colorimetric assays were determined by laser diffractometry and using reflection spectrometer, respectively. Sensory analysis was performed with 25 semitrained panelists, using a 5-point hedonic scale. The results showed that viscoelastic properties, flow behavior parameters, particle size, and color parameters (L*, a*, and b*, where L* represents lightness, a* represents the redness/greenness quality of the color, and b* represents the yellowness and blueness quality of the colors) were significantly affected by the concentration of the gum tragacanth and the severity of this effect was influenced by the type of gum. The use of appropriate type and concentration of gum tragacanth in date milk formulation can improve the texture and mouth feel by affecting on particle size and the flow behavior of this product.
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Heating a methylcellulose solution forms a thermal-reversible hydrogel. After the hydrogel forms, its properties change according to its temperature. However, the effects of heating this solution during storage and then cooling it are unclear. We investigated the effects of this heating and cooling on rheological and drug release characteristics. We prepared samples of methylcellulose solution (2% methylcellulose and 20% D-sorbitol) and examined them under two conditions: 1) storage for 24 hours at 4 to 30℃, 2) storage for 24 hours at 4 to 50℃, then cooling to 4℃ and maintained for 4 hours. We performed rheological investigations of viscosity, gelation temperature and gel strength, and examined the drug release characteristics by using a diffusion cell method with acetaminophen as the model drug. It was found that as the storage temperature rose, the methylcellulose solution increased in viscosity and the gelation temperature and gel strength changed. During storage at 30℃, the amount of drug released by the solution increased and the diffusion coefficient was high. When cooled to 4℃, the solution recovered its viscosity, gelation temperature, gel strength and drug release characteristics, regardless of the previous storage temperature. These results clarify that although the rheological and drug release characteristics of methylcellulose solution change with changes in storage temperature, the original characteristics are recovered after the solution is cooled to 4℃ and maintained at that temperature for four hours.
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This article presents the development and evaluation of a new topical formulation of diclofenac diethylamine (DDA) as a locally applied analgesic lotion. To this end, the lotion formulations were formulated with equal volume of varying concentrations (1%, 2%, 3%, 4%; v/v) of permeation enhancers, namely propylene glycol (PG) and turpentine oil (TO). These lotions were subjected to physical studies (pH, viscosity, spreadability, homogeneity, and accelerated stability), in vitro permeation, in vivo animal studies and sensatory perception testing. In vitro permeation of DDA from lotion formulations was evaluated across polydimethylsiloxane membrane and rabbit skin using Franz cells. It was found that PG and TO content influenced the permeation of DDA across model membranes with the lotion containing 4% v/v PG and TO content showed maximum permeation enhancement of DDA. The flux values for L4 were 1.20±0.02 μg.cm(-2).min(-1) and 0.67 ± 0.02 μg.cm(-2).min(-1) for polydimethylsiloxane and rabbit skin, respectively. Flux values were significantly different (p < 0.05) from that of the control. The flux enhancement ratio of DDA from L4 was 31.6-fold and 4.8-fold for polydimethylsiloxane and rabbit skin, respectively. In the in vivo animal testing, lotion with 4% v/v enhancer content showed maximum anti-inflammatory and analgesic effect without inducing any irritation. Sensatory perception tests involving healthy volunteers rated the formulations between 3 and 4 (values ranging between -4 to +4, indicating a range of very bad to excellent, respectively). It was concluded that the DDA lotion containing 4% v/v PG and TO exhibit the best performance overall and that this specific formulation should be the basis for further clinical investigations.
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The isoflavone genistein (GEN) is a natural product with potential applications for skin cancer treatment and chemoprevention; however its high lipophilicity and chemical instability limits its clinical use. Therefore, attempts towards protecting GEN against degradation and increasing its penetration in the skin might be a valid approach. In this work, GEN loaded-PLA nanocapsules (GEN-NC) were prepared by interfacial deposition of preformed polymer (nanoprecipitation); physicochemical characterization and stability studies for 90 days were conducted. GEN-NC were incorporated into semi-solid formulations and permeation experiments were carried out using porcine ear skin. GEN-NC optimized formulation presented a mean diameter of 139 +/- 7.31 nm, polydispersity index of 0.128 +/- 0.08, encapsulation efficiency of 89.63 +/- 2.27% and drug loading from 0.6 to 1.4 w/w%. Stability studies demonstrated that nanocapsules did not exhibit aggregation during the 90 days of the assay, however, a drop in encapsulation efficiency was observed in the first 10 days. Permeation experiments demonstrated that a higher amount of GEN reaches deeper layers of the skin and increased penetration was achieved when GEN-NC were incorporated in a semi-solid gel formulation, indicating that GEN-NC might be a promising nanocarrier system for skin delivery of GEN.
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Thermosensitive hydrogel containing drug-loaded liposomes delivery system offers the possibility of reduced dosing frequency and sustained drug action. In the study, a soluble chitosan derivative, N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride, was used and interacted with glycerophosphate to produce a thermosensitive hydrogel as the matrix of doxorubicin-loaded liposomes. The formulation could retain the liquid state with good fluidity below or at room temperature for long time but turn into a nonflowing gel after exposing to body temperature for no more than 5 min. The mean size of liposomes was increased when dispersed into the hydrogel, while the entrapment efficiency of doxorubicin in liposomes was not discounted by the hydrogel, which was over 90%. The in vitro release experiment performed with a dialysis membrane model showed that the liposomes-containing hydrogel exhibited an excellent sustained-release behavior, which eliminated the initial burst release occuring in the liposomal formulation and only released about 22% loaded drug in 9 days. In vivo antitumor activity was evaluated by the survival time of H22-bearing mice treated with various doxorubicin formulation, which showed that the hydrogel enhanced the antitumor activity and reduced the systemic toxicity. Thus, all these results demonstrated that the thermosensitive hydrogel with embedded liposomes is a promising antitumor drug carrier for topical cancer therapy.
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Niosomes play an increasingly important role in drug delivery as they can reduce toxicity and modify pharmacokinetic and bio-availability. Topically applied niosomes can increase the residence time of drugs in the stratum corneum and epidermis, while reducing the systemic absorption of the drug. It can act as drug containing reservoirs and the modification of the vesicular compositions or surface properties can adjust the drug release rate and the affinity for the target site. Ketoconazole is a broad spectrum Imidazole derivative useful in the treatment of superficial and systemic fungal infections. In order to improve the low skin penetration and to minimize the side effects associated with topical conventional drug administration, Ketoconazole niosomes were prepared by a thin film hydration method using different ratios of non-ionic surfactants (Span 40, 60 and Tween 60) along with cholesterol (CHO). The formulations were evaluated for size, shape, entrapment efficiency and in vitro drug release. Niosomes appeared spherical in shape and size range was found to be 4.86 ± 1.24-7.38 ± 3.64 μm. The entrapment efficiency was found in the range of 55.14 ± 2.29-78.63 ± 0.91% and in vitro drug release in the range of 46.63 ± 0.95-72.37 ± 0.59% in 24 h. Ketoconazole niosomes formulated with Span 60 and CHO in the ratio of 1:0.2 were found to be promising and were incorporated into 1% Carbopol gel. The formulated gel was evaluated for various physicochemical parameters and antifungal activity. The in vitro drug release study was carried out using phosphate buffer saline pH 7.4 and was found to be 36.18 ± 1.50% in 12 h. Gel formulation containing niosomes loaded with Ketoconazole showed prolonged action than formulations containing Ketoconazole in non-niosomal form and it can be developed successfully to improve the antifungal activity.
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Physicochemical properties of chiral ibuprofen are significant to formulation scientists because its enantiomers and eutectics possess lower melting points than its racemate. The influence of these properties on transdermal formulation development, especially the relative effect of lowered melting point, on skin permeation must be carefully assessed to provide the most efficacious formulation. Thermodynamic properties and crystalline structures of the enantiomers, eutectics, and racemate of chiral ibuprofen were investigated by differential scanning calorimetry and X-ray powder diffraction. The effect of melting point lowering on membrane permeation rates was mathematically modeled. Model was validated by in vitro skin permeation experiments using different preparations of racemic ibuprofen, enantiomer, and eutectic. Both enantiomer and eutectic formed a two-phase liquid system containing an emulsifiable aqueous phase and an oily phase in the presence of aqueous isopropyl alcohol (aIPA). The eutectic emulsion had the highest permeation rate, a 2.21-fold increase in flux compared with saturated aIPA solutions of the racemate with a 2.03-fold increase in flux. Results from the two-phase liquid system supported those from the mathematical models, albeit somewhat lower, and confirmed their use in predicting maximum flux utilizing thermodynamic data. Study data also supported the idea that eutectic formation, for ibuprofen and probably other chiral drugs, may be one of the best ways to develop topical formulations for improved percutaneous absorption to avoid the use of permeation enhancers or synthetically modifying chemical structure. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
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To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e. Candida albicans (C. albicans) and Rhodotorula sp. Four Algeria honeys of different botanical origin were analyzed to test antifungal effect against C. albicans, and Rhodotorula sp. Different concentrations (undiluted, 10%, 30%, 50% and 70% w/v) of honey were studied in vitro for their antifugal activity using C. albicans and Rhodotorula sp. as fungal strains. The range of the diameter of zone of inhibition of various concentrations of tested honeys was (7-23 mm) for Rhodotorula sp., while C. albicans showed clearly resistance towards all concentrations used. The MICs of tested honey concentrations against C. albicans and Rhodotorula sp. were (70.09-93.48)% and (4.90-99.70)% v/v, respectively. This study demonstrates that, in vitro, these natural products have clearly an antifungal activity against Rhodotorula sp. and C. albicans.
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To evaluate the additive action of ginger starch on the antifungal activity of honey against Candida albicans (C. albicans). C. albicans was used to determine the minimum inhibitory concentration (MIC) of four varieties of Algerian honey. Lower concentrations of honey than the MIC were incubated with a set of concentrations of starch and then added to media to determine the minimum additive inhibitory concentration (MAIC). The MIC for the four varieties of honey without starch against C. albicans ranged between 38% and 42% (v/v). When starch was incubated with honey and then added to media, a MIC drop was noticed with each variety. MAIC of the four varieties ranged between 32% honey (v/v) with 4% starch and 36% honey (v/v) with 2% starch. The use of ginger starch allows honey benefit and will constitute an alternative way against the resistance to antifungal agents.
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Ultrapotent topical corticosteroids are the mainstay of psoriasis treatment, used either alone or in combination with a topical vitamin D analog. Traditionally used in an ointment vehicle for psoriasis, clobetasol propionate 0.05% is also available in spray, foam, lotion, and shampoo formulations, which may provide for improved convenience and acceptance in many patients with similar efficacy, safety, and tolerability as the traditional ointment and cream formulations. To compare newer formulations with traditional ointment and cream formulations, we performed a systematic review of the literature. Search terms included 'clobetasol propionate,' combination with 'psoriasis,' 'vasoconstriction,' ' vasoconstrictor,' or 'absorption' for each of the four vehicles ('spray,' 'foam,' 'lotion,' and 'shampoo'). While there are very few direct comparison studies between clobetasol propionate in different vehicles, the efficacy rates (with success defined as clear or almost clear of psoriasis) for more recent formulations are high, with most patients achieving success after 2-4 weeks of treatment in well controlled clinical trials, with response rates that are similar to those with the traditional clobetasol propionate ointment. Small differences in vasoconstrictor potency or cutaneous absorption have been noted among the formulations, but the clinical significance of these observations is difficult to discern. Recent research has emphasized the importance of treatment adherence in the management of psoriasis. Adherence to treatment is likely to be a far more important determinant of success than are small differences in drug delivery, especially in actual clinical use as opposed to the well controlled environment of clinical trials. For patients who prefer a less messy vehicle, adherence and outcomes are likely to be better with the more recent formulations compared with the traditionally recommended ointment.
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AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. METHODS: The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. RESULTS: After one course of treatment with liniment levamisole, the levels of CD3⁺, CD4⁺, and the ratio of CD4⁺/CD8⁺ increased as compared to those before the treatment but the level of CD8⁺ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B. Keywords: Liniment levamisole, Chronic hepatitis B, Cellular immune function, T lymphocyte subsets, mIL-2R Citation: Wang KX, Zhang LH, Peng JL, Liang Y, Wang XF, Zhi H, Wang XX, Geng HX. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. World J Gastroenterol 2005; 11(45): 7208-7210
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Cycloferon, a prospective interferon inductor, and the mechanism of its action were characterized. Its formulation for external use as liniment was developed. The pharmacotherapeutic effect of the drug in the treatment of paradontitis was shown. The drug efficacy in herpetic lesions of the mouth and lips mucosa was observed. The use of cycloferon in the treatment of the buccal mucosa affections in HIV-infected subjects was substantiated.
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The aim of the study was to estimate the efficacy of liniment cycloferon included in combined therapy of herpetic infection in 30 patients with psoriasis divided into 2 groups. Combined treatment of patients with recurrent herpetic infection promoted elimination of general infection syndrome, shortened duration of eruption and local inflammation, accelerated epithelization of herpetic erosion, and decreased the frequency of relapses during the follow-up.
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The efficiency of cycloferon liniment in combined treatment of herpetic infection in patients with latent form of HIV infection has been assess by observations of 40 patients divided into two groups. In the first group, the standard treatment was supplemented with the application of cycloferon liniment twice a day during 7 days; in the second group, the therapy was conducted according to standard recommendations. It was established that the application of cycloferon liniment in combination with standard therapy in patients with relapse of herpetic infection against the background of HIV infection ensures faster disappearance of general infectious syndrome, decreases the period of eruptions and the duration of local inflammations, and accelerates the epithelialization of erosions.
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We characterised biological properties of novel formulations of two low-potency glucocorticosteroids, dexamethasone and hydrocortisone, which have an equivalent dose ratio of 1:50 in vasoconstriction tests. The rate of such carrier-mediated, mainly non-diffusive glucocorticosteroids transport with very deformable lipid vesicles (Transfersomes®) through the skin, and the corresponding cutaneous drug biodistribution data, were complemented with the drug bio-efficacy studies. The minimum effective drug dose that reduces arachidonic acid-induced murine ear oedema by 50% was used as one bioactivity indicator. The minimum drug amount ensuring such an effect in mouse skin decreases appreciably when a corticosteroid is applied epicutaneously with very deformable vesicles rather than a lotion or a crème. Specifically, the minimum effective dose for hydrocortisone in very deformable carriers is 2–3 μg cm−2 whereas for the crème- or lotion-like preparations at least 10 μg cm−2 is required. Such three- to fivefold relative increase of hydrocortisone potency is accompanied by at least 13%, and more often >20%, absolute drug potency enhancement. The delivery of hydrocortisone with very deformable carriers moreover prolongs the suppression of the drug-induced oedema nearly 2-fold (to ∼24 h per application). The effective dose of dexamethasone delivered with very deformable vesicles into murine skin is reduced >10 times compared with the crème- or lotion-based products. Specifically, less than 0.1 μg cm−2 dexamethasone in very deformable vesicles suppresses the arachidonic acid-induced murine ear oedema >50%, on the average. Dexamethasone use on the skin in such vesicles extends the duration of drug action fourfold, compared with a commercial crème, i.e. to >48 h per application. Epicutaneous use of glucocorticosteroids in very deformable vesicles also diminishes such drug's abrasion sensitivity and may increase the general robustness of drug effect. Lower frequency of skin treatment, which ensures adequate biological response, is a result of this. Topical corticosteroid delivery with very deformable vesicles, Transfersomes®, thus improves the therapeutic risk–benefit ratio, arguably due to better targeting into and longer drug presence in the skin.
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Abstract The clinical use of halobetasol propionate (HP) is related to some adverse effects like irritation, pruritus and stinging. The purpose of this work was to construct HP-loaded solid lipid nanoparticles (HP-SLN) formulation with skin targeting to minimizing the adverse side effects and providing a controlled release. HP-SLN were prepared by solvent injection method and formula was optimized by the application of 3(2) factorial design. The nanoparticulate dispersion was evaluated for particle size and entrapment efficiency (EE). Optimized batch was characterized for differential scanning calorimetry (DSC), scanning electron microscopy, X-ray diffraction study and finally incorporated into polymeric gels of carbopol for convenient application. The nanoparticulate gels were evaluated comparatively with the commercial product with respect to ex-vivo skin permeation and deposition study on human cadaver skins and finally skin irritation study. HP-SLN showed average size between 200 nm and 84-94% EE. DSC studies revealed no drug-excipient incompatibility and amorphous dispersed of HP in SLN. Ex vivo study of HP-SLN loaded gel exhibited prolonged drug release up to 12 h where as in vitro drug deposition and skin irritation studies showed that HP-SLN formulation can avoid the systemic uptake, better accumulative uptake of the drug and nonirritant to the skin compared to marketed formulation. These results indicate that the studied HP-SLN formulation represent a promising carrier for topical delivery of HP, having controlled drug release, and potential of skin targeting with no skin irritation.
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Chitosan, a β-1,4-linked polymer of glucosamine with lesser amounts of N-acetylglucosamine, has well-recognized hemostatic properties. Chitosan is also able to open tight cellular junctions, facilitating paracellular drug transport and delivery. Chitosan, through topical application, facilitates the systemic delivery of analgesic drugs. Theoretically this ability could be used to enhance the local delivery of hemostatic drugs, such as tranexamic acid, improving chitosan's role as a topical dressing. Individually a chitosan-dextran gel and tranexamic acid have been shown to improve hemostasis after endoscopic sinus surgery. A combination of both should lead to improved hemostasis and better postsurgical outcomes. The use of a chitosan/tranexamic acid dressing could have a wide range of potential beneficial applications in a number of other clinical surgical settings. While the initial main application might be as an improved external hemostatic dressing, it should also be useful on a range of internal surgical wounds.
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Assessment of skin uptake and clearance are important to determine the efficiency and systemic safety of dermatological formulations. The objective of this study was to assess the skin uptake, clearance and possible systemic delivery of ciclopirox following topical application in wistar rats. In vitro studies (3 h) were carried out in excised pig skin to assess the permeation and retention capacity of ciclopirox in skin layers using gel formulations (1 and 2% w/v). In vivo dermatopharmacokinetics (DPK) parameters were determined by measuring the drug levels in the skin as a function of time post application (0.5, 1, 1.5 and 2 h) and post removal (3, 4, 6 and 8 h) of the formulation in wistar rats. The plasma drug concentrations were also determined in same animals. In vitro data indicates low permeability and high retention of ciclopirox in the stratum corneum. DPK data observed indicate higher Cmax value (175.43 ± 25.62 µg/cm(2) ) and AUC (632.14 ± 102.26 µg.h/cm(2) ) with 2% (w/v) gel formulation. Further, the skin elimination of ciclopirox follows first order kinetics with a short half-life (t1/2 ~2 h). The fraction of drug reaching systemic circulation was found to be significantly low (~0.15% of the applied dose). A relation between the drug concentration in the skin layers and the plasma was observed with a short lag period. The topical availability of ciclopirox was found to be relatively low and endured rapid clearance with minimal systemic uptake. This article is protected by copyright. All rights reserved.
Article
Abstract The aim of this study was to develop liposomal-based (LBGF) and micro-emulsion-based (MBGF) gel formulations of croconazole to compare their topical delivery potential. Conventional gels were also prepared using various polymers such as sodium carboxymethyl cellulose (SCMC), Poloxamer 407, Carbopol 971P and chitosan. The in vitro release of croconazole from conventional gel formulations, LBGF and MBGF were carried out using cellophane membrane as permeation membrane. However, in vitro skin permeations studies of all formulations were carried out using rat skin. The results of the drug release/skin permeation studies indicated that the highest release was obtained from SCMC followed by chitosan, Poloxamer 407 and finally Carbopol 971P gel. Therefore, liposomes and micro-emulsions were loaded on Carbopol 971P gel. The drug release and skin permeation of croconazole from different LBGF and MBGF showed that MBGF had superior release/permeation than LBGF. MBGF having ethanol as co-surfactant showed higher release/permeation of drug than MBGF-containing propylene glycol. The analysis of data according to different kinetic models indicated that the release of drug from different LBGF and MBGF followed the Higuchi model. The antimicrobial activity of the different LBGF and MBGF of croconazole was carried out by measuring the inhibition zone (mm) and compared by the effect of miconazole cream as control. The different LBGF and MBGF showed an excellent activity against different species of fungi as compared with miconazole cream. Overall, these results indicated that developed LBGF and MBGF could have great potential for topical delivery of croconazole.
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The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection has significantly increased. Generally, the success of this bacterium as a pathogen is attributed to its ability to adhere to surfaces and remain there, under the protection of an extracellular matrix known as biofilm. To combat MRSA with regular doses of vancomycin, efforts are continuously underway to increase its effectiveness. A promising technique is to use combinational therapeutics. In vitro experiments showed that farnesol can be used as an adjuvant with conventional antibiotics. Farnesol is a natural sesquiterpenoid and quorum-sensing molecule. The biggest obstacle to using this concept is that farnesol is highly water insoluble. This compromises its bioavailability if it were to be used along with vancomycin at the site of infection when the treatment needs to be administered in vivo. Herein we designed an efficient therapeutic strategy for the simultaneous delivery of both antibiotic and adjuvant in order to treat MRSA infections. We demonstrate that sufficient quantities of both vancomycin and farnesol can be incorporated into sol-gel silica applied as thin films on an implant surface. The incorporation of the hydrophobic farnesol does not affect the stability of the thin films and neither does it affect the controlled release of vancomycin. The data demonstrate the potent adjuvant effect of farnesol on vancomycin in inhibiting MRSA infection. In vitro experiments show the complete inhibition (10(6) fold reduction in growth compared to control) of methicillin-sensitive S.aureus (MSSA) and methicillin-resistant S.aureus (MRSA) when the ratio of vancomycin to farnesol in the sol-gel silica films is optimized. The local delivery of antibiotics minimizes the need for systemic antibiotics. The incorporation of vancomycin and farnesol into thin sol-gel films represents a new treatment paradigm for the topical delivery of antibiotics with adjuvant. The potential clinical benefits are significant and include avoiding the need for revision surgery, preventing surgical site infection and controlling healthcare costs.
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Intranasal delivery is one of the most interesting and challenging endeavors facing pharmaceutical scientists. The conventional nasal drug delivery systems including solutions, suspensions, and ointments show drawbacks such as short residence in the nasal cavity, highly variable efficiency, low permeability, and inconvenient administration. In situ gel-forming systems are an interesting polymeric system that exists as flowing aqueous solution before administration and undergoes phase transition to form a viscoelastic gel in a physiologic environment. Benefiting from the merits of both a solution and a gel, an impressive number of in situ gel-forming systems induced by temperature, pH, and ions have been prepared for use in nasal drug delivery in the past few years. In situ gel-forming systems increase the retention of drugs in the nasal cavity, and some of them also show permeation-enhancing capabilities. This article reviews the in situ gel-forming systems used for nasal drug delivery and introduces their gelling mechanisms and other favorable features for intranasal delivery. It also describes the release patterns and drug stability of in situ gels as well as their in vivo performances and local safety following nasal administration.
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The stimuli-sensitive hydrogel is an injectable formulation that is used to deliver drugs, cells, and genes into the body. Hydrogels are available in various physical forms such as solid molded, pressed powder matrix, microparticle, coating, or membrane forms. The network structure of hydrogels can be macroporous, microporous, or nonporous. Different categories of biomaterials, such as natural, synthetic, and combinations (e.g., semisynthetic such as natural-natural, natural-synthetic, and synthetic-synthetic polymers), are commonly used in hydrogel preparation. Classification of hydrogels mainly depends upon physical stimuli (temperature, electric fields, solvent composition, light, pressure, sound, and magnetic fields) and chemical or biochemical stimuli (pH, ions, and specific molecular recognition events). Several approaches for the synthesis of hydrogels have been reported, including emulsification, micromolding, photolithography, isostatic ultra high pressure, and microfluidic techniques. Hydrogels provide structural integrity and cellular organization, serve as tissue barriers, act as bioadhesive and drug depots, deliver bioactive agents and cells, and possess unique swelling properties and stru