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Transdermal Drug Delivery Systems
... [1] An additional method of administering medications through the skin layer is transdermal drug delivery [2,3]. Before the medication reaches the intended location, it passes through the skin and enters the bloodstream, where it circulates throughout the body [2,3]. ...
... [1] An additional method of administering medications through the skin layer is transdermal drug delivery [2,3]. Before the medication reaches the intended location, it passes through the skin and enters the bloodstream, where it circulates throughout the body [2,3]. Oral administration systems have many drawbacks despite these benefits, including low drug stability in the gastrointestinal tract and susceptibility to first pass metabolism. ...
Many noninvasive administrations have recently e merged as alternatives to conventional needle inject ions.The transdermal drug delivery system (TDDS) , which has a low rejection rateremarkable ease of a dministration, and remarkable patient convenience and persistence, is the most alluring of all.TDDS m ay be useful not only in the pharmaceutical industr y but also in the skin care industry, which includes cosmetics. Because this method focuses on local administration, it can prevent local drug concentration accumulation and nonspecific drug distribution to tissues that are not the medication's target. There has been a lot of research on techniques to overcome the various physicochemical properties of the skin that hinder transdermal delivery. In this review, we enumerate the several types of TDDS methodologies now in use and critically analyze their unique advantages and disadvantages, characterization methods, and potential.Research on these alternative ways has advanced, demonstrating the high efficiency of TDDS, and it is expected that these technologies will be used in many different industries
... Transdermal drug delivery is an alternative way of delivering drugs via the skin layer [1,2]. The drug is carried through the skin into the bloodstream and circulates systemically in the body before reaching the target site [1,2]. ...
... Transdermal drug delivery is an alternative way of delivering drugs via the skin layer [1,2]. The drug is carried through the skin into the bloodstream and circulates systemically in the body before reaching the target site [1,2]. The transdermal drug delivery method has several advantages over other routes of administration. ...
Transdermal patches are a non-invasive method of drug administration. It is an adhesive patch designed to deliver a specific dose of medication through the skin and into the bloodstream throughout the body. Transdermal drug delivery has several advantages over other routes of administration, for instance, it is less invasive, patient-friendly, and has the ability to bypass first-pass metabolism and the destructive acidic environment of the stomach that occurs upon the oral ingestion of drugs. For decades, transdermal patches have attracted attention and were used to deliver drugs such as nicotine, fentanyl, nitroglycerin, and clonidine to treat various diseases or conditions. Recently, this method is also being explored as a means of delivering biologics in various applications. Here, we review the existing literatures on the design and usage of medical patches in transdermal drug delivery, with a focus on the recent advances in innovation and technology that led to the emergence of smart, dissolvable/biodegradable, and high-loading/release, as well as 3D-printed patches.
... In which twin measured release effect is gained where the emulsion is either oil in water or vice versa that is incorporated in the gel base. In simple words, emulgels are defined as emulsions in gel [44]. In an emulsion, the medicate particles are consolidated within the inside stage, acting as sedate supply from where the sedate passes through the outside stage and to the skin and get ingested [45]. ...
... Properties like non-toxicity, less irritability, and non-unfavorably susceptibility should be present [23]. They ought to show favorable compatibility with the drugs and the excipients added [44]. When it is removed from the skin, barrier properties should return rapidly [35]. ...
Background:
Emulgels are the emerging drug delivery system nowadays that has become popular for the delivery of hydrophobic drugs. This formulation is considered a novel type of drug delivery system and a mixture of emulsion and gel. Objective: The objective of this review is to throw light on the preparation of emulgels and their evaluation which will conclude how important these dosage forms are. In the coming years, it will be most commonly used because it is easy to use and enhances patient compliance. Conclusion: Emulgels are easily removable, spreadable, thixotropic, greaseless, have a pleasing appearance, emollient, long shelf life, and transparent. In the present era, the emulgels are being used for the delivery of many drugs like analgesics, anti-inflammatory, anti-acne and anti-fungal. Hence, it is of great pharmacological importance and is relatively free of side effects.
... Versatility and Flexibility: Transdermal patches can be used for a wide variety of therapeutic applications, including pain management, hormone replacement therapy, smoking cessation, cardiovascular treatment, and neurological disorders. Their versatility makes them suitable for delivering both small and large molecules, including peptides and proteins, which are typically challenging to administer via oral routes (Chien, 1992). ...
Transdermal patches have emerged as a cutting-edge technology in drug delivery systems, providing a non-invasive, controlled, and patient-friendly method for administering medications. These patches deliver drugs through the skin and into the bloodstream, bypassing the gastrointestinal tract and first-pass metabolism, thereby improving bioavailability and reducing systemic side effects. This review offers an in-depth examination of the formulation and development of transdermal patches, focusing on the critical components and materials used in their construction, including active pharmaceutical ingredients, polymer matrices, permeation enhancers, adhesives, backing layers, and release liners. The development process of transdermal patches is meticulously outlined, covering stages from preformulation studies and formulation development to prototype creation, in vivo studies, clinical trials, regulatory approval, scale-up, and market launch. Each step is essential for ensuring the safety, efficacy, and quality of the final product. Furthermore, this review addresses the common challenges encountered in the formulation and development of transdermal patches, such as overcoming the skin's barrier properties, selecting appropriate drug candidates, ensuring proper adhesion, maintaining stability, and managing patient variability. Strategies to overcome these challenges, including the use of chemical and physical permeation enhancers, innovative adhesive technologies, and rigorous clinical testing, are discussed in detail. By providing a comprehensive overview of the formulation and development of transdermal patches, this review aims to enhance understanding of the complexities involved in creating these advanced drug delivery systems.
... Transdermal drug transport is an additional technique for delivering medication through the cutaneous bed 1,2 . The medication enters the bloodstream through the epidermis and travels across the body's systems before arriving at the intended location 1,2 . ...
... [2,3] Transdermal drug delivery can closely mimic the slow intravenous infusion, without its potential hazards and also offer another most important advantage in allowing the patient to terminate the drug therapy by simply removing the patch at any desired time if toxicity develops. [4][5][6][7] The drug applied topically is distributed following absorption, first into the systemic circulation and then transported to the target tissue, which can be relatively remote from the site of drug application to achieve its therapeutic action. [8] Carvedilol is a potent beta-adrenergic blocking agent commonly used in hypertension, leftventricular dysfunction, and several other cardio-vascular disorders. ...
The purpose of this research work was to develop and evaluate transdermal patches of Carvedilol employing different ratios of hydrophilic polymers by solvent evaporation technique. The main objective is to avoid first pass effect and to improve bioavailability. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy. The results suggested no physicochemical incompatibility between the drug and the polymers. Nine formulations consisting of Hydroxy propyl methyl cellulose k4M, Sodium cmc, xant han gum, in the ratios 1:1, 1:2, 1:3 were prepared. The prepared TDDS were evaluated for in vitro drug release, moisture absorption, moisture loss and mechanical properties. The patches coded as F 1 , F 2 , F 3 (HPMCk4m) showed maximum release of 93.54%, 95.42%, 97.54% and F 4 , F 5 , F 6 (Sodium cmc) showed maximum release of 92.67%, 94.76%, 96.74% and F 7 , F 8 , F 9 (xanthan gum) showed maximum release of 98.89% ,92.75%, 86.35% within 12 hrs. The formulation F 7 emerging to be ideal formulation for Carvedilol. The results followed Korsmeyer-peppas kinetics (R 2), and the mechanism of release was either by diffusion or erosion. The stability studies were carried out on the most satisfactory formulations F 7 and there was no significant difference in the physicochemical parameters, and in in-vitro drug release profiles.
... An additional method of administering medications through the skin layer is transdermal drug delivery [2]. The medication enters the bloodstream through the epidermis and travels across the body's systems before arriving at the intended location [3]. ...
In transdermal drug delivery, the property of protecting barriers of the skin plays a role of major issue as skin does not allow passing the drug. The complex structure of skin is responsible for this issue. The present review was based on the recent updates on transdermal patches. An additional method of administering medications through the skin layer is transdermal drug delivery. A transdermal patch is a medicated patch that can be applied topically to provide medication at a specified rate directly into the bloodstream via the layers of skin. Actually, the most practical way to administer is via patches. In general, there are four main types of transdermal medical patches (drug-in adhesive, reservoir, matrix, and micro-reservoir systems). It concluded that transdermal patches hold promise as a convenient and efficient drug delivery method for a range of conditions; however, there are a number of obstacles that need to be addressed. These include the potential for self-inflicted toxicity due to incorrect dosing, poor adhesion, low drug penetration, potential trigger for skin irritation, or patch failure. In order to maximise the safety and effectiveness of this delivery system, all of this calls for additional study and development.
... Процессы высвобождения ЛВ из ЛФ -таблеток, капсул, трансдермальных терапевтических систем (ТТС), пленок или гелей -в биологическую среду традиционно сопоставляют с процессами растворения ЛВ в биологической системе [3,4]. В связи с этим высвобождение основывается на тестах оценки растворимости ЛВ. ...
Introduction. The review considered the basic concepts of drug release and kinetic modeling of this process from dosage forms (DF) according to the dissolution profile using a vertical Franz diffusion cell.
Text. Drug release from dosage forms (ointments, gels, transdermal patches and polymer films) is usually described as the processes of drug dissolution in the biological system. Formally, this process, in accordance with pharmacopoeial methods, is assessed using various solubility tests. The theoretical aspects of drug release are based on the theory of mass transfer of substances from a polymer matrix into a system that simulates a biological environment. Drug release can be carried out via the passive diffusion mechanism according to Fick and "non-Fick" diffusion, drug desorption from the inner side of the membrane, as well as other mechanisms. Drug release is determined both lipophilicity and the membrane nature, both various physicochemical parameters of the drug. One of the correlation characteristics of mass transfer is the assessment of the permeability coefficient for a specific membrane that simulates skin. Permeability coefficient describes the rate of penetration of a drug per unit concentration in distance/time units. An example of relationship of "structure-permeability" correlation are the equations relating the permeability constant and lipophilicity to the molecular weight of the drug. The paper showed statistical methods of data analysis (MANOVA, ANOVA) and model-dependent methods (zero order, first order, Higuchi model, Korsmeyer – Peppas model, Hixson – Crowell model, etc.). The ideal drug delivery of non-degradable and non-disaggregating drugs describes as drug release model by zero-order reaction. For drug release of water-soluble drugs from a porous matrix, first-order reaction model is more typical. Kinetic models of fractional power functions are used usually as the cube root law (Hixson – Crowell model) or the square root law (Higuchi model) to describe the process of drug release from gels and dermal films and patches. The Korsmeyer – Peppas model allows us to evaluate the mechanism of mass transfer with Fickian diffusion or another process.
Conclusion. Mathematical modeling of the drug release kinetics from soft dosage forms is an important element for the development and optimization of their compositions. The study of the drugs release from soft dosage forms, including TTS and polymer films, as well as the release from solid dosage forms, is based on establishing correlations between the kinetics of the release and dissolution profile. The main release models, regardless of the DF, remain the following models: zero order, first order, Korsmeyer – Peppas, Higuchi, Hickson – Crowell, the empirical or semi-empirical constants of which vary significantly depending on the DF and the release mechanism (Fickian diffusion or another drug mass transfer mechanism). Correlation relationships QSPeR or QSPR, using the coefficients of permeability, diffusion and lipophilicity, provide information on the mass transfer of drugs through the skin.
... Protection is one of them, but it is also involved in the immune system, thermal regulation, and even molecular synthesis [1]. Skin can be used as a gateway for medical applications, for example transdermal drug delivery, where the molecules released can be systemically absorbed into the bloodstream [2][3][4]. ...
The delivery of therapeutical molecules through the skin, particularly to its deeper layers is impaired due to the stratum corneum layer, which acts as barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consists on an array of microscale needles. This particular biomedical device had been drawing attention due to their ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size and composition. The design process of a microneedle device must take in account several factors, like the location delivery, the material and manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application, cosmetics, therapy, diagnosis, tissue engineering, sample extraction, cancer research, wound healing, among others.
... Most recently, there is an increasing recognition that the skin can also serve as the port of administration for systemically active drugs. In this case, the drug applied topically will be absorbed first into blood circulation and then be transported to target tissues, which could be rather remote from the site of drug application, to achieve its therapeutic purpose (1) . Recently, it is becoming evident that the benefits of I.V. drug infusion can be closely duplicated, without its hazards, by using the skin as the port of drug administration to provide continuous transdermal drug infusion into the systemic circulation. ...
Aim:-The present study is to formulate the matrix type transdermal patches of Nebivolol hydrochloride as a model drug with combination of HPMC K100M and ERS-100 to minimize the dose of the drug for lesser side effect. Method:-Matrix type transdermal patches containing Nebivolol hydrochloride were prepared using two polymers by solvent evaporation technique. Aluminium foil cup method was used as a substrate. Polyethylene glycol (PEG) 400 was used as plasticizer and Dimethyl sulfoxide was used as penetration enhancer. Major Results:-The physicochemical parameters like weight variation, thickness, folding endurance, drug content, Percentage moisture absorption and Percentage moisture loss were evaluated. All prepared formulations indicated good physical stability and no skin irritation. In-vitro drug release and drug permeation studies of formulations were performed by using Franz diffusion cells. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in-vitro skin permeation through rat skin (Wistar albino rat) as compared to all other formulations. Conclusions:-On the basis of in vitro drug release through skin permeation performance, Formulation F1 was found to be better than other formulations and it was selected as the optimized formulation.
... The vertical diffusion cells include the same basic parts as a donor and an acceptor compartment and a membrane between the two compartments ( Figure 3), but in the literature, a different semantic structure is available to avoid the entrapping bubble or minimize human intervention [114][115][116]. The acceptor compartment usually contains a buffer and a magnetic stirrer at the bottom of the device, which helps to ensure homogeneous distribution. ...
Bioavailability assessment in the development phase of a drug product is vital to reveal the disadvantageous properties of the substance and the possible technological interventions. However, in vivo pharmacokinetic studies provide strong evidence for drug approval applications. Human and animal studies must be designed on the basis of preliminary biorelevant experiments in vitro and ex vivo. In this article, the authors have reviewed the recent methods and techniques from the last decade that are in use for assessing the bioavailability of drug molecules and the effects of technological modifications and drug delivery systems. Four main administration routes were selected: oral, transdermal, ocular, and nasal or inhalation. Three levels of methodologies were screened for each category: in vitro techniques with artificial membranes; cell culture, including monocultures and co-cultures; and finally, experiments where tissue or organ samples were used. Reproducibility, predictability, and level of acceptance by the regulatory organizations are summarized for the readers.
... This method of administration is especially useful for drugs that are quickly eliminated from the body 4 . Absorption through the skin can be enhanced by suspending in an oily vehicle and rubbing the resulting preparation into the skin 5 . ...
The purpose of this research was to develop a desired topical formulation containing clotrimazole for treatment of fungal infections like eczema, itching, pruritis etc. Topical formulation enriched with SLN of clotrimazole were prepared. The solid lipid nanoparticulate dispersion of clotrimazole was prepared by hot homogenization technique using polymers like Carbopol 934, mannitol and PEG 6000. The nanoparticulate dispersion was evaluated for various parameters such as physical evaluations, particle size, diffusion studies, DSC, SEM, stability studies. The solid lipid nanoparticulate dispersion showed mean particle size less than 1000 nm. Differential scanning Calorimetry studies revealed no drug excipient incompatibility. Diffusion studies release profile of clotrimazole from nanoparticulate dispersion showed prolonged drug release. And all other evaluations were found to be complied the limits. Thus it can be concluded that formulation of SLN containing clotrimazole can be successfully formulated to localize the drug in the skin for to treat topical fungal infections.
... Transdermal Drug Delivery (TDD) is undoubtedly an eloquent well-renowned dosage system developed as a drug laden gel or film that delivers the drug into the skin to reach systemic circulation by active or passive diffusion/permeation. Transdermal patches govern the transportation of drugs at a controlled manner by exerting a proper hydrophilic-lipophilic polymer mixture (Chien, 1987;Mukherjee et al., 2005;Walters, 1999). The drug may either be loaded in matrix of a polymeric film or accumulated in a reservoir that requires porous release membrane (Ghanghoria et al., 2013). ...
... In the last 20-30 years, there has been a steady increase in systemic fungal infections, not only by known pathogenic fungi but also by fungi previously thought to be innocuous and are termed opportunistic infections. (2) The techniques generally employed to enhance the solubility of poorly water soluble drugs are use of surface active agents, hydrates and solvates, polymorphism, complexation, hydrotropic solubilization and conventional trituration and grinding. Among these techniques, hydrotrope solubilization is considered as easy method of solubilization.Hydrotropes are class of compounds that normally increase the aqueous solubility of insoluble solutes (3,4). ...
... DRUGS [3,7,8,9,10,11] Routes available for the administration of protein and peptide drugs are include: To achieve a stable, safe and effective nasal delivery of peptides and proteins, these limitations have to be overcome. Incorporating excipients in the formulation and the design of novel nasal dosage systems are exciting approaches, but these areas still require further exploration to be of real clinical and commercial benefit. ...
The protein and peptides are very important in biological cells. Lack of proteins and peptides causes diseases like Diabetes mellitus. Diabetes mellitus is caused due to the lack of protein called insulin. Now a day"s r-DNA technology and hybridoma techniques also used in protein and peptide based pharmaceuticals. Proteins are the most abundant macromolecules in the living cells, occurring in all cells and all parts of cells. Cells can produce proteins that have strikingly different properties and activities, by joining same 20 amino acids in many different combinations and sequences. The term protein is used for molecules composed of over 50 amino acids, and peptide for molecules composed of less than50 amino acids. Scientific advances in molecular and cell biology have resulted in the development of two new biotechnologies. The first utilizes recombinant DNA to produce protein products. The second technology is hybridoma technology. Various proteins and peptides drugs are epidermal growth factor, tissue plasminogen activator. Management of illness through medication is entering a new era in which a growing number of biotechnology produced peptide and protein drugs are available for therapeutic use. Ailments that can be treated effectively by this new class of therapeutic agents include cancers, memory impairment, mental disorders, and hypertension. Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly employed method of administration for therapeutic proteins and peptides. This article summarizes the application of polymeric NPs for protein and peptide drug
... Also, these leave a sticky and greasy feel after application leading to poor patient compliance. Therefore, there is a need for development of a dosage form which permits less frequent dosing by maintaining a close contact with the skin for prolonged time period thereby improving the patient compliance [3][4][5][6]. ...
... Transdermal drug delivery systems are devices containing drug of defined surface area that delivers a pre-determined amount of drug to the surface of intact skin at a pre-predefined rate. 1 The skin as a route for systemic drug administration has become very attractive since the introduction of transdermal therapeutic systems in the form of patches. 2 The discovery of transdermal drug delivery systems (TDDS) is a breakthrough in the field of controlled drug delivery systems. The ability of TDDS to deliver drugs for systemic effect through intact skin while bypassing first pass metabolism has accelerated transdermal drug delivery research in the field of pharmaceutics. ...
Transdermal drug delivery systems are devices containing drug of defined surface area that delivers a predetermined amount of drug to the surface of intact skin at a pre-predefined rate. The skin as a route for systemic drug administration has become very attractive since the introduction of transdermal therapeutic systems in the form of patches. The discovery of transdermal drug delivery systems (TDDS) is a breakthrough in the field of controlled drug delivery system Transdermal dosage forms, alternative to the conventional dosage form are becoming very popular because of their unique advantages. Like controlled zero ordered absorption, simple mode of administration and having option to terminate the action in case of adverse effect. So the TDDS makes them desirable for the treatment of chronic diseases where long term treatment is necessary. Scopolamine, clonidine, nitroglycerine, antihypertensive, hypoglycemic, antiischaemic, drug molecules being extensively used in transdermal form. This article is dedicated to the review of transdermal recent research in the area of antiischaemics, antihypertensive, antiemetic, hormones, opioids, anticholinergics and other drug molecules which should be selected for TDDS reported in various pharmaceutical journals.
... and (iii) unstable in the intestinal environment 8,9 . Sacubitril is an antihypertensive drug used in combination with valsartan 10 .The combination drug valsartan/sacubitril, marketed under the brand name Entresto, is a treatment for heart failure 11 . ...
Floating Drug Delivery Systems (FDDS) have a bulk density lower than gastric fluids and thus remain buoyant in the stomach for a prolonged period of time, without affecting the gastric emptying rate. While the system is floating on the gastric contents, the drug is released slowly at a desired rate from the system. These floating tablets mainly prepared for reduction of lag time and release the drug up to 12 hours and may also increase the bioavailability of the drugs by utilizing the drug to full extent avoiding unnecessary frequency of dosing. The purpose of this research was to develop and evaluated floating matrix tablets of sacubitril and valsartan. The floating matrix tablets of sacubitril and valsartan were prepared by direct compression method using altered concentrations of HPMC K4M, HPMC K100M, sodium alginate as polymers and sodium bicarbonate, citric acid as gas generating agent. FTIR, DSC studies conformed that there was no incompatibility between the polymers and the drug. Tablet preformulation parameters were within the pharmacopoeias limit. Tablets were evaluated by different parameters such as weight uniformity, content uniformity, thickness, hardness, in vitro release studies, buoyancy determination and kinetic analysis of dissolution data. The varying concentration of gas generating agent and polymers was found to affect on in-vitro drug release and floating lag time. Tablet showed ≤ 1min lag time, continuance of buoyancy for >12 h. The in-vitro drug release pattern of sacubitril and valsartan optimized floating tablets (F16) was fitted to different kinetic models which showed highest regression (r2 = 0.9838) for Higuchi model. The Optimized formulation (F16) showed no significant change in physical appearance, drug content, floating lag time, in vitro dissolution studies after 75%±5% RH at 40±20C relative humidity for 6 months. Prepared floating tablets of sacubitril and valsartan may prove to be a potential candidate for safe and effective controlled drug delivery over an extended period of time for gastro retentive drug delivery system.
... The structure of oral sustained release systems is subject to several inter related variables of considerable importance such as the kind of delivery system, the illness being treated, the patient, the length of treatment and the properties of the medication. [3] Ondansetron hydrochloride (OND HCl) is a serotonin 5-HT3 receptor antagonist and is an extensively exploit drug for the treatment of several remedial purposes like antiemetic particularly it is utilized in the prevention of post-operative sickness and vomiting and chemotherapy induced unsettled stomach and nausea or radiation induced queasiness and sickness. The main drawback of conventional dose of OND HCl is its oral bioavailability, which is about 60% and it has short biological half life which required frequent dosing (three times a day) led to patient incompliance. ...
The objective of proposed work was to develop Ondansetron Hydrochloride (OND HCl) sustained release matrix tablets for the better treatment of vomiting for extended period of time. Sustained release matrix tablet is the drug delivery system that is designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of single dose. The matrix tablets of OND HCl were prepared by direct compression method using varying ratio of hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose. The bends of tablets were evaluated for bulk and tapped density, % compressibility index and angle of repose and powder of all formulations blend exhibited that low interparticle friction and excellent flow characteristics. The prepared matrix tablets were then assessed for different physical tests like consistency of weight, thickness, hardness, friability, drug content and in vitro drug release. Each batch of the OND HCl matrix tablets were of good quality as to hardness, thickness, friability and % medicament content. The in vitro drug release study was done for 2 hours by utilizing paddle technique in 0.1N HCl (pH 1.2) as dissolution media and 6 hours using phosphate buffer (pH 6.8) as dissolution media. The drug release study showed that all formulation FMT-1, FMT-2, FMT-3, FMT-4, FMT-5 and FMT-6 were provide the drug release on sustained manner up to 8 hrs. Amongst the developed matrix tablets formulations, FMT-2 containing ethyl cellulose (100 mg) was optimized as best because FMT-2 show highest drug release profile and promoting the sustained release of drug, which could potentially improve the patient compliance.
... However, solid dosage forms are popular because of the ease of administration, accurate dosage, self-medication, pain avoidance, and most importantly the patient compliance. 1 Tablets and capsules are the most popular solid dosage forms. However, many people face difficulty in swallowing tablets and hard gelatin capsules. ...
Now-a-days, Orodispersible drug delivery systems are extensively used to improve bioavailability and patient compliance. Over the past three decades, Orodispersible tablets (ODTs) have gained considerable attention as a preferred alternative to conventional tablets and capsules due to better patient compliance, improved solubility and stability profiles. ODTs are solid dosage forms containing medicinal substances which disintegrate rapidly, usually in a matter of seconds, when placed on the tongue. New ODT technologies address many pharmaceutical and patient needs, ranging from enhanced life-cycle management to convenient dosing for paediatric, geriatric, and psychiatric patients with dysphagia. The therapeutic activity of these formulations is obtained through a typical manner like disintegration followed by dissolution. Hence disintegration has major role for facilitating drug activity. In recent years, several newer agents have been developed known as superdisintegrants. The objective of the present article is to highlight the various kinds of superdisintegrants (Natural & Synthetic) along with their role in tablet disintegration and drug release, which are being used in the formulation to provide the safer, effective drug delivery with patient compliance. Keywords: ODTs, Orodispersible tablets, Disintegrants, Superdisintegrants, Natural, and Synthetic.
... Poly (vinyl alcohol), PVA, belongs to the group of polymers which can be used in combination with other non-biodegradable polymers for tuning the required properties in the resultant composite blend. It is one of the synthetic, biodegradable, biocompatible, water-soluble polymers utilized in medical applications such as wound dressings [1] artificial skin, coatings, [2] Transdermal patches, [ 3 ] cardiovascular devices , [4][5][6] and drug delivery systems. Moreover, it has good barrier ( 141 properties against scents, oils, and fats. ...
In this study, different weight percent of poly(vinyl alcohol) (PVA)/ poly(vinyl pyrrolidone)(PVP)/ Cellulose (CELL) blend solutions were prepared by solution blending followed by preparing ofpolymer metal complexes with Ag (I), Cu (II), Ni (II) and Co(II). Antibacterial properties wereevaluated by dilute method against five pathogenic bacteria (Escherichia coli, Klebsiella pneumonae ,Pseudomonas aeruginasa,, Staphylococcus aureus , Staphylococcus Albus ) . Polymer metal complexesshowed different activities against the various microbial isolates. The polymer blend metal complexesshowed higher activity than the free polymer blends
... The adhesive is usually a pressure-sensitive adhesive (PSA), which is defined as a material which adheres to a substrate with light pressure and, ideally, leaves no residual adhesive upon its removal. It is one of the most critical components of the patch [13,18]. The PSA must adhere to the substrate, be biocompatible as well as compatible with the drug and excipients, remain stable and functional once formulated in the patch, provide adequate diffusivity to the drug, and be acceptable to the regulatory authorities [13]. ...
Nail patches have a potential role as drug carriers for the topical treatment of nail diseases such as onychomycosis, a common condition. Our aim was therefore to develop a systematic and novel approach to the formulation of a simple drug-in-adhesive ungual patch. Twelve pressure-sensitive adhesives (PSAs), four backing membranes, two release liners and three drugs were screened for pharmaceutical and mechanical properties. From this initial screening, two PSAs, two drugs, one backing membrane and one release liner were selected for further investigation. Patches were prepared by solvent-casting and characterised. The patches had good uniformity of thickness and of drug content, and showed minimal drug crystallisation during six months of storage. Meanwhile, the drug stability in the patch upon storage and patch adhesion to the nail was influenced by the nature of the drug, the PSA and the backing membrane. The reported methodology paves the way for a systematic formulation of ungual nail patches to add to the armamentarium of nail medicines. Further, from this work, the best patch formulation has been identified.
... Poly (vinyl alcohol), PVA, belongs to the group of polymers which can be used in combination with other non-biodegradable polymers for tuning the required properties in the resultant composite blend. It is one of the synthetic, biodegradable, biocompatible, water-soluble polymers utilized in medical applications such as wound dressings [1] artificial skin, coatings, [2] Transdermal patches, [ 3 ] cardiovascular devices , [4][5][6] and drug delivery systems. Moreover, it has good barrier ( 141 properties against scents, oils, and fats. ...
In this study, different weight percent of poly(vinyl alcohol) (PVA)/ poly(vinyl pyrrolidone)
(PVP)/ Cellulose (CELL) blend solutions were prepared by solution blending followed by preparing of polymer metal complexes with Ag (I), Cu (II), Ni (II) and Co(II). Antibacterial properties were evaluated by dilute method against five pathogenic bacteria (Escherichia coli, Klebsiella pneumonae , Pseudomonas aeruginasa,, Staphylococcus aureus , Staphylococcus Albus ) . Polymer metal complexes showed different activities against the various microbial isolates. The polymer blend metal complexes showed higher activity than the free polymer blends.
... Delayed release systems, function by maintaining the drug within the dosage form for some time before release. [3] Commonly the release rate of drug is not altered and does not result in sustained delivery once drug release has begun. Successful fabrication of extended release products is usually difficult & and involves consideration of physicochemical properties of drug, pharmacokinetic behavior of drug, route of administration, disease state to be treated and, most importantly, placement of the drug in dosage form total will provide the desired temporal and spatial delivery pattern for the drug. ...
The aim of design of oral extended drug delivery system is to achieve a prolonged therapeutic effect by continuously releasing medicament over an extended period of time after administration of a single dose. An attempt was made to formulate Tramadol Extended Release (ER) matrix tablet using combination of hydrophobic and hydrophilic polymer consisting of ethyl cellulose, HPMC K15M, carbopol, and xanthan gum. The polymeric concentration of hydrophobic and hydrophilic polymer was optimized and was found that drug to polymeric ratio (hydrophobic and hydrophilic) of 1:0.75:0.75 was appropriate for the formulation of Tramadol ER tablet. The concentration of hydrophobic polymer was kept constant were as the combination of hydrophilic polymer was attempted and combined to hydrophobic polymer to retard the drug release for 24-hour from the matrix tablet. A total of nine formulations (F1-F9) of Tramadol matrix tablet, with different concentration of hydrophobic and hydrophilic polymer were used with other excipients. The tablets were compressed by direct compression method after subjecting the blend to blend physical parameters studies like studies like angle of repose, bulk density, tapped density, Carr’s index. The results obtained were satisfactory. Post compression parameters like hardness, weight variation, friability, drug content analysis and in-vitro release profiles of drug from all the formulations could be best expressed by Higuchi’s equation, as the plots showed high linearity (R2: 0.942-0.995). To confirm the diffusion mechanism, the data were fit into Korsmeyer equation. The formulations F-1 to F-6 showed good linearity (R2: 0.961 to 0.993), which indicate the mechanism is diffusion coupled with erosion.
... Topical drug delivery systems are designed to deliver a drug formulation to the skin for the treatment of cutaneous disorder or the cutaneous manifestations of a general disease such as psoriasis with the aim of restricting the pharmacological effect of the drug to the 1 surface of the skin or within the skin. The advantages of topical dosage forms over oral forms include the ease of application and withdrawal of medication, avoidance of First Pass effect, maintenance of activity for a prolonged 2 period and reduction of potential side effects. Pharmaceutical creams are typical examples of topical drug delivery systems and the most common are oil-inwater emulsion systems, whose structure or semisolid character is dependent upon emulsified liquid droplets 3 or particles that make up the internal phase. ...
ABSTRACT
Background: Phyllanthus amarus Schum and Thonn (Euphorbiaceae) is a plant of ethnomedicinal importance
whose cream formulations have shown antimicrobial properties in a previous study.
Objective: To determine the quantitative effects of formulation additives on the physicochemical and
antimicrobial properties of Phyllanthus amarus cream.
Methods: The ethanol extract of Phyllanthus amarus was prepared by maceration for 72 hours and the cream
formulated and assessed using established procedures. The individual and interaction effects of nature (N) of
humectant, concentration (C) of humectant and extract concentration (E) on the physicochemical and in vitro
3
antimicrobial properties of the cream formulation were determined using a 2 factorial experimental design.
Results: The independent coefficient values ranked N>C >E on viscosity, E>N>C on globule size and C >E > N on
spreadability. The ranking on antibacterial property was E > N > C, while on fungi it changed to E > C > N. The
physicochemical properties of the formulations were differently influenced by N, C and E. The individual and
interaction effects on the physicochemical and antimicrobial properties were found to be significant (p<0.05).
Conclusion: In the design of P. amarus cream, careful consideration of formulation variables is required to
obtain optimum physicochemical and antimicrobial properties.
Keywords: Phyllanthus amarus cream, formulation variables, factorial experimental design
... MODELS FOR TRANSDERMAL PERMEATION 2,8,11,15 Along the course of skin permeation, a drug molecule will encounter a number of diffusional resistance which counteract its permeation through various skin tissue layers. The total diffusional resistance (R s ) that a drug molecule has to overcome during the course of permeation across the skin tissues and the subsequent uptake by the capillary network for transport to the general circulation is described mathematically by: ...
... Poly (vinyl alcohol), PVA, belongs to the group of polymers which can be used in combination with other non-biodegradable polymers for tuning the required properties in the resultant composite blend. It is one of the synthetic, biodegradable, biocompatible, water-soluble polymers utilized in medical applications such as wound dressings, 7 artificial skin, 8 coatings, 9 Transdermal patches, 10 cardiovascular devices, [11][12][13][14] and drug delivery systems. 15 Moreover, it has good barrier properties against scents, oils, and fats. ...
Silver has been used as an antimicrobial since the 1800s. But since the discovery of systemic antibiotics in the early 20th century, the use of silver had declined. In the last two decades, with advent of nanotechnology, interest in silver for wound treatment resurged, since silver is efficacious for killing the antibiotic resistant bacteria strains. Silver releasing dressings and patches are increasingly in demand for treatment of infected wounds.23 Along with Silver, ZnO and TiO2 nanoparticles also have high level of antimicrobial activity and have been included in this study. Nanocomposites of PVA-MFR with ZnO/TiO2/Ag as films and coatings that promise to be good polymeric material with wide range of antimicrobial applications are being reported. This gives us the advantage of using lesser concentration of nanoparticles in an inherent antimicrobial material PVA-MFR, so as to reach a desired level of antimicrobial efficacy, yet minimizing possibility of any toxicity by using lower concentrations of nanoparticles. Bacterial infection from medical devices is a major problem in hospitals,25 and so these polymeric antimicrobial coatings could probably be exploited to modify the surface of medical devices.
... The oral route of drug administration is very common for systemic effects. Tablet or capsule is the most widely used dosage form because of convenience in the ease of administration, accuracy of dosing and patient compliance (1,2). Tablets are unit solid dosage forms meant for oral use and are manufactured from blend of powders containing the active pharmaceutical ingredient (API) and other additives to be compressed into a tablet which could be prepared by either wet granulation, dry granulation or direct compression. ...
... Transdermal drug delivery is the topical application of drugs to the skin in the treatment of skin diseases, wherein high concentrations of drugs can be localized at the site of action, thereby reducing the systemic drug levels and side effects [1][2][3]. 'U.S. Emerging Transdermal Drug Delivery Technologies Markets', reveals that this market generated revenues worth $1.57 billion in 2002 and reached a staggering $5.67 billion in 2009 [4]. In 1924, Rein proposed that a layer of cells joining the STRATUM CORNEUM-the thin, outermost layer of the skin-to the EPIDERMIS posed the major resistance to transdermal transport [5]. ...
Human skin is a remarkably efficient barrier, designed to keep ‘‘our insides in and the outsides out’’. This barrier
property causes difficulties for transdermal delivery of therapeutic agents. One long-standing approach to increase
the range of drugs that can be effectively delivered via this route has been to use penetration enhancers, chemicals
that interact with skin constituents to promote drug flux.
To-date, a vast array of chemicals has been evaluated as penetration enhancers (or absorption promoters), yet
their inclusion into topical or transdermal formulations is limited since the underlying mechanisms of action of these
agents are seldom clearly defined. In this article we review some uses of the more widely investigated chemical
penetration enhancers and discuss possible mechanisms of action.
... Microneedle (MN) devices are currently attracting great interest in transdermal drug/vaccine delivery and patient monitoring (Donnelly et al., 2014aDonnelly et al., , 2012b Mooney et al., 2014; Prausnitz 2004; Quinn et al., 2014; Yang et al., 2013). These systems are composed of an array of micron-sized needles that painlessly, and without drawing blood, pierce and bypass the outermost layer of the skin, the stratum corneum (SC), which is the principal barrier to transdermal drug delivery (Benson and Watkinson, 2012; Hadgraft, 2002; Prausnitz et al., 2004). MN arrays create micro-conduits through the SC that can be used to deliver drugs to the deeper layers of the skin from where they can be absorbed directly into the systemic circulation, or to deliver vaccines to the skin-resident antigen-presenting cells (Donnelly et al., 2012b; Tuan-Mahmood et al., 2013). ...
The use of biological tissues in the in vitro assessments of dissolving (?) microneedle (MN) array mechanical strength and subsequent drug release profiles presents some fundamental difficulties, in part due to inherent variability of the biological tissues employed. As a result, these biological materials are not appropriate for routine used in industrial formulation development or quality control (QC) tests. In the present work a facile system using Parafilm M® (PF) to test drug permeation performance using dissolving MN arrays is proposed. Dissolving MN arrays containing 196 needles (600μm needle height) were inserted into a single layer of PF and a hermetic "pouch" was created including the array inside. The resulting system was placed in a dissolution bath and the release of model molecules was evaluated. Different MN formulations were tested using this novel setup, releasing between 40 and 180μg of their cargos after 6hours. The proposed system is a more realistic approach for MN testing than the typical performance test described in the literature for conventional transdermal patches. Additionally, the use of PF membrane was tested either in the hermetic "pouch" and using Franz Cell methodology yielding comparable release curves. Microscopy was used in order to ascertain the insertion of the different MN arrays in the PF layer. The proposed system appears to be a good alternative to the use of Franz cells in order to compare different MN formulations. Given the increasing industrial interest in MN technology, the proposed system has potential as a standardised drug/active agent release test for quality control purposes.
Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient’s skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs.
The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others.
Due to their extended shelf life, enhanced drug solubilization, and simplicity in preparation and administration, microemulsions are among the greatest possibilities for new drug delivery systems. Microemulsions are liquid mixtures of amphiphile, water, and oil that are thermodynamically stable and optically isotropic. They have become cutting-edge drug delivery systems that enable controlled or sustained release for parenteral, ophthalmic, percutaneous, topical, and transdermal medication administration.Because of their low viscosity, transparency, and, more precisely, their thermodynamic stability, microemulsions may be easily distinguished from regular emulsions. Microemulsions have a wide range of uses and applications, including in the pharmaceutical, agrochemical, cutting oil, biotechnology, food, and cosmetic industries as well as in analytical applications and environmental detoxification. This review paper's main goal is to talk about using microemulsions as a medicine delivery mechanism with other potential uses.
This dynamic system is dependent on polymer wetting, hydration and dissolution for Controlled release of drug. At the same time other soluble recipients or drug substance will also wet, dissolve, and diffuse out of the matrix, whereas insoluble excipients or drug substance will be held in place until the surrounding polymer, excipients, drug complex erodes or dissolves away. By using two different hydrophilic polymers such as hydroxypropyl cellulose or hydroxy propyl methyl cellulose were tried for the formulation of SR of cyclobenzaprine tablet. The sustained release tablet was formulated by wet granulation technique. The cyclobenzaprine, extended release polymers, solubilizing agent, diluents are passed through Sieve no. 24, with the help of Blender these materials are kept for dry mixing at slow speed which leads to the formation for uniform matrix system. Non aqueous system is for the formation of granules such as Iso propyl alcohol along with the polyvinyl pyrrolidone K30 act as a binder, which leads to the formations of granules, the wet screening that wet mass, granules kept for drying in the dehumidifier environment for sufficient time. The matrix system had a low weight variation and high mechanical strength, the drug release profile was within the limit of USP acceptance criteria.
The main objective of this work is to formulate and evaluate Cetirizine HCl MFDT’s using different concentrations of superdisintegrants like croscarmellose sodium (CCS), sodium starch glycolate (SSG) and their combinations in different ratios. The in vitro disintegration time of Cetrizine Hcl prepared by direct compression method by super disintegrates were found to be in the range of 18 to 11sec fulfilling the official requirements. The bulk density and tapped bulk density for the entire formulation blend varied from 0.508 gm/cc to 0.5438 gm/cc and 0.5941 to 0.6408 respectively. The friability was found in all designed formulations in the range 0.42 to 0.74% to be well within the approved range (<1%). The weight variation was found in all designed formulation in the range 97 to 102 mg. The wetting time were found to be in the range of 11 to 18sec. Water absorption ratio for all the formulations found in the range 11 to 16%.combination of sodium starch glycolate and cross carmellose sodium (6% of 25%-ssg&75%ccs)) promotes dissolution rate of drug release when compared to formulation of SSG & CCS alone. It may be due to capillary and wicking mechanism of SSG & CCS. Keywords:
The poultice formulation is a patch containing a large amount of water. It is known that the water contained in the adhesive polymer layer (ADPL) of poultice affects the cooling sensation and skin permeability of the active pharmaceutical ingredient (API). In this study, we evaluated the relationship between the water content in a ketoprofen poultice formulation and the amount of time the poultice was left out at room temperature after removal from the airtight container, as well as the influence of the decreasing water content on the skin permeability of the API. After removing the poultice from the container for 1 h, the mass of the ADPL decreased by approximately 40%. When the near-infrared (NIR) spectrum of the ADPL of poultice was measured, the peaks reflecting the hydroxyl group were attenuated depending on the time left out at room temperature. It is suggested that the changes in the mass and NIR spectrum of the ADPL are caused by the change in the water content. Moreover, when the permeability of API was evaluated on hairless mouse skin, the cumulative skin permeation amount and flux decreased, while the lag time was prolonged as the time left out increased. These results suggest that the skin permeability of the API is impaired by water evaporation and that maintaining the water in the ADPL in poultice is very important from not only the viewpoint of cooling sensation, tackiness and moisturizing but also the skin permeability of the API.
Graphical Abstract Fullsize Image
The skin, commonly considered to be the largest organ of the human body, has been used as a drug delivery route for numerous dermal and transdermal drugs. Being a structural barrier protecting the underlying tissues, the skin poses many challenges to be used as an amenable passage for drugs to permeate. In this chapter, we would describe the current advantages and disadvantages of transdermal drug delivery, making comparisons with different drug delivery routes, elucidate the mechanisms of passive and active transdermal drug delivery and deliberating different formulations which can be delivered via the transdermal route. We would investigate the current status and the development of microneedles, a strategy invented to transiently breach the skin’s stratum corneum to deliver drugs through the skin. We would also investigate the different types of microneedles, provide insights into the microneedles used in clinical trials and diffusion cell systems used to assess the efficacy of microneedles in their capacity to deliver drugs through the skin.
This chapter aims to present the main microneedle/nanoparticle (MN/NP) combinatory approaches developed to date. It describes main types of nanocarriers used for passive permeation through the stratum corneum (SC). The SC layer has been described as the main barrier to the penetration of most drugs and nanomedicines (NMs). The main types of lipid nanoparticles are solid lipid nanoparticle (SLNs) and nanostructured lipid carrier (NLCs). The chapter focuses on optimisation of the permeation of NPs and MPs when used in combination with MNs. It discusses the therapeutic applications of the combinatory technology. The chapter shows the potential of this type of MN for vaccine delivery and the delivery of nanoencapsulated drugs. It also focuses on early synergistic developments of nanomedicine with MN technology, in an effort to provide a comprehensible and conversant understanding of the niche scientific area.
Background: Guggul, the gum resin obtained from Commiphora mukul, is one of the components of various formulations of traditional Ayurvedic medicine to treat inflammation, atherosclerosis, and weight loss. This research work describes Guggul lipid as a carrier and synergistic effect for anti-inflammatory drugs.
Method: Guggulosomes prepared by trituration method was further incorporated into carbopol gel, developed for the enhanced topical drug delivery system for the phenylbutazone. This preparation was characterized by using Attenuated total reflection- Fourier transform infrared spectroscopy (ATR-FTIR), Scanning electron microscopy (SEM), Atomic force microscopy (AFM), Differential scanning calorimeter (DSC), Thermogravimetric analysis (TGA), Particle size & Zeta potential and further guggulosomes was tested for Anti-inflammatory activity and % cumulative drug release. All these study was carried out by using standard protocol.
Results: The guggulosomes shows all the characteristic peaks in ATR-FTIR. The optimized formulation was spherical in shape having diameter >200 nm. The % entrapment efficiency was 77.2 ± 0.212 with good % Cumulative drug release 60.80 ± 0.707%. The anti-inflammatory activity of the optimized formulation was found satisfactory (89%).
Conclusion: The guggulosomes prepared by trituration method was found to give a synergistic effect along with the phenylbutazone when incorporated into the carbopol gel. Thus, this present research shows that it can be good perspective for enhanced topical drug delivery system.
Oral routes are most commonly preferred route for delivering drug. Most common oral dosage forms are tablet and capsules. But many patients such as geriatric, pediatric and dysphasic patients find difficult to swallow conventional tablet and capsule. To overcome various problems related to swallowing, Fast dissolving Tablets (FDTs) were designed in early 19th century and hence further advancement has led to development of Fast Dissolving Oral Films (FDOFs). In the recent years, many of the pharmaceutical groups are focusing their research on rapid dissolving technology. Amongst the plethora of avenues explored for rapid drug releasing product, FDOFs technology is gaining much attention. These are solid dosage forms, which disintegrate or dissolve within 1 min when placed in the mouth without drinking water or mastication. This technology has been used for local action as well as rapid release products. The fast dissolving oral films are formulated using various Active pharmaceutical ingredients (API), film forming polymers, plasticizer, flavors, colors and sweeteners. Initially FDOFs are up to breath strips, confection and oral care markets. But now it became a novel and widely accepted technology for delivering OTC and prescription medication too.Sunsari Technical College Journal 2015, 2(1):58-68
We present a novel multi-pathway, mass balance based, fate and exposure model compatible with life cycle and high-throughput screening assessments of chemicals in cosmetic products. The exposures through product use as well as post-use emissions and environmental media were quantified based on the chemical mass originally applied via a product, multiplied by the product intake fractions (PiF, the fraction of a chemical in a product that is taken in by exposed persons) to yield intake rates. The average PiFs for the evaluated chemicals in shampoo ranged from 3×10(-4) up to 0.3 for rapidly absorbed ingredients. Average intake rates ranged between nano- and micrograms per kilogram bodyweight per day; the order of chemical prioritization was strongly affected by the ingredient concentration in shampoo. Dermal intake and inhalation (for 20% of the evaluated chemicals) during use dominated exposure, while the skin permeation coefficient dominated the estimated uncertainties. The fraction of chemical taken in by a shampoo user often exceeded, by orders of magnitude, the aggregated fraction taken in by the population through post-use environmental emissions. Chemicals with relatively high octanol-water partitioning and/or volatility, and low molecular weight tended to have higher use stage exposure. Chemicals with low intakes during use (<1%) and subsequent high post-use emissions, however, may yield comparable intake for a member of the general population. The presented PiF based framework offers a novel and critical advancement for life cycle assessments and high-throughput exposure screening of chemicals in cosmetic products demonstrating the importance of consistent consideration of near- and far-field multi-pathway exposures.
Transdermal drug delivery systems are also known as patches, containing dispersed or dissolved drug with plasticizers, polymers etc., are intended to deliver a therapeutically effective amount of drug across the skin. Main objective of the present work is to develop transdermal patches of Valsartan with hydrophilic and hydrophobic polymers containing the drug reservoir by solvent evaporation method. Valsartan is a poorly soluble drug with poor bio availability. In this experiment, the membranes of ethylcellose and Eudragit RS 100 and Eudragit RL 100 along with HPMC combination were used to achieve controlled release of the drug. The prepared patches showed satisfactory physiochemical characteristics of weight variation, thickness, folding endurances, moisture absorption and drug content. Results for in-vitro permeation studies were done by using Franz diffusion cell with cellophane membrane. The effect of non- ionic surfactant like tween 80 and span 80 on drug permeation were studied. Based on the kinetic studies, the patch containing both HPMC and Eudragit RS100 showed satisfactory drug release patterns.
Most people accept that green tea is well-known as a medicinal plant. It is alwayssuggested for daily health promotion. Moreover, its extracts have been widely used astopical applications for wound-healing, anti-aging, and disease treatments. Catechins arethe prominent compounds in green tea extract and are promising ingredients indermatological products. They are highly reactive with other compounds, such as reactiveoxygen species and biologic macromolecules to scavenge free radicals or initiatebiological effects. Although green tea presents an excellent result in in vitrostudies withpromising activity to benefit human health, the result of in vivo studies has not been fullysatisfied. A few clinical studies reported that green tea extract significantly improved skinelasticity and increased the dermis's thickness; thus, providing skin wrinkle relief. Theskin inflammation induced by UV radiation was decreased substantially when pretreatingthe skin with green tea extract. Many researchers have attempted to explain thecause of skin improvement by several mechanisms. However, the complete picture hasnot been established. On the other hand, some studies revealed that topical formulation ofgreen tea extract could not improve skin nourishing, and skin moisture tended to decreasewhen applying green tea products for a long time. The discrepancy of the in vivo studyresults is due to the limitation of catechins' properties. Instability, less skin permeation,and cutaneous metabolism play a crucial role in the effectiveness of green tea application.Although green tea's benefits for the skin seem unsatisfied in real life, a recent studyrevealed that the appropriate preparation of green tea formulation and deliverytechnology can diminish catechin limitations.
Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.
Recently, a great extent of R & D interests and attention have been generated aiming to the optimization and prolongation of drug administration via the controlled release mechanisms of novel drug delivery systems (1,2).
The release of melatonin, estradiol, and flourogestone acetate from subdermal implants was enhanced when implants were fabricated from silicone elastomers containing co-solvents. This enhancement followed a Q vs. t relationship. As glycerol concentration increased, the increments in release rate were greater for hydrophilic drugs than for hydrophobic drugs. When drug loading in the implants was held constant, release rates were found to be a function of glycerol concentrations in the device. A synergistic enhancement of release rate was observed when both glycerol and sodium chloride were added to the silicone matrix. The fact that co-solvents enhance the rate of drug release from silicone elastomers indicates that a reduction in the activation energy required for drug release may occur.
A mathematical model was developed to correlate the drug permeation rate through the skin with the drug release rate from a matrix-type drug delivery system. Experiments were carried out using hairless mouse abdominal skin mounted on a recently-developed and hydrodynamically well-calibrated Keshary-Chien skin permeation system. A matrix-type drug delivery system was designed to contain different loading doses of nitroglycerin and to study the effect of drug loading variation on the rate of drug release, the rate of skin permeation and the equilibrium concentration of nitroglycerin in the skin.
Results indicated that the stratum corneum plays a significant rate-limiting role in the skin permeation of nitroglycerin across the intact skin, yielding a constant skin permeation profile. The permeation rate across the intact skin was observed to increase with the increase in the drug release flux initially and then levelled off in a hyperbolic fashion. Various constants were obtained from the reciprocal plot of skin permeation rate vs. drug release flux. These constants could be used for the prediction of the skin permeation rate. A very good correlation between the predicted and the observed values of skin permeation rates was observed.
After the stratum corneum was removed by stripping technique, the mechanism and the rate of skin permeation became dominated by the mechanism and the release rate of the delivery system.
A linear correlation was observed between the drug permeation rate through the skin and the equilibrium concentration of drug in the skin. This correlation was observed in both intact and viable skins.
Based on sorption and permeation characteristics of scopolamine in human skin in vitro and drug elimination kinetics obtained from pharmacokinetic studies, a mathematical model was developed for estimating and optimizing the temporal pattern of scopolamine delivery from a transdermal therapeutic system through human skin in vivo. Experimentally measured scopolamine delivery in vivo conformed to this model.
The efficacy of transdermal clonidine, alone and in combination with diuretics, has been demonstrated in several studies involving patients with mild to moderate essential hypertension. In one 3-month open study, 64% of patients (wearing one to three 3.5 cm2 transdermal patches) achieved sustained blood pressure reductions throughout the treatment period. In this large study, side effects requiring discontinuation of drug were not observed. Transdermal clonidine reduced plasma renin activity and urinary aldosterone excretion to the same extent as that reported for oral clonidine. Renal function or serum electrolytes were not affected during therapy with transdermal clonidine. Another study showed that patients receiving oral clonidine and hydrochlorothiazide experienced comparable blood pressure reductions when switched to transdermal patches. Plasma drug concentrations measured during treatment with the transdermal patches were similar to the trough levels observed during treatment with oral clonidine. The equipotency of oral and transdermal therapy in combination with hydrochlorothiazide was also demonstrated in two remaining studies. In one of these studies it was suggested that daily variations in blood pressure induced by the peak and trough drug levels of the oral form were minimized by the stable drug levels characteristics of the transdermal device.
To determine whether the nonoral administration of estradiol (E2) might provide physiologic replacement without alteration of hepatic function, 20 postmenopausal women were studied before and after 3 weeks of treatment with either E2-containing transdermal therapeutic systems or placebo. Twenty premenopausal women were also studied. With E2-containing systems, serum E2 and estrone levels were restored to the premenopausal range. Variable responses of the different biochemical and biologic markers of the actions of E2 were observed. The most sensitive marker was vaginal cytology, with the E2 dosage reverting the maturation index to premenopausal values. Hot flashes, measured objectively, were reduced in frequency but not abolished. Serum levels of follicle-stimulating hormone and luteinizing hormone were lowered but remained higher than the premenopausal range. No significant changes were noted in urinary calcium/creatinine and hydroxyproline/creatinine ratios, which were used as markers of bone resorption. With active systems, no significant changes were noted in the concentrations of the hepatic proteins renin substrate and thyroxine-binding globulin or in the binding capacities of cortisol-binding globulin and sex hormone-binding globulin. These results indicate that transdermal E2 administration may be used to provide estrogen replacement while exerting limited effects on hepatic function.
This article describes in vitro and in vivo performance of two transdermal drug delivery systems. Transderm -Nitro delivers nitroglycerin for the treatment and prevention of angina for 24 hours following a single application. In a three-way crossover study comparing Transderm -Nitro with two other transdermal nitroglycerin products, mean plasma levels of drug were similar 0.5 and 6 hours after application; however, with Transderm -Nitro the area under the plasma concentration curve was highest and the coefficient of variation was least. A transdermal therapeutic system for delivering clonidine ( Catapres -TTS) is used for the treatment of hypertension. In a two-way crossover study comparing Catapres -TTS and oral Catapres , plasma levels of clonidine with use of the transdermal system reached a steady-state value in 2 to 3 days and remained steady for the duration of the wearing period; plasma levels with oral Catapres , however, fluctuated markedly. The ratio of maximum to minimum plasma levels during a dosing interval was 2 for oral Catapres and approximately 1 for Catapres -TTS. The potential use of intact skin as a route of entry for controlled delivery of drugs to the systemic circulation is promising.
Male fertility has reportedly been regulated by the long-term, continuous administration of testosterone. To deliver the testosterone at a controlled rate for a month or longer, a bandage-type, testosterone-releasing, disk-shaped device was developed. In vitro drug elution studies demonstrated that a constant release profile of testosterone was achieved. In vivo studies in rhesus monkeys with the medicated device directly overlaying the navel for 46 d, yielded a fairly steady plasma level and also a constant urinary excretion rate for 32 d. A greater systemic bioavailability (more than twofold) was achieved as compared with drug disposition directly onto the navel or via the placebo device (i.e., drug is deposited onto the prefabricated placebo device). A fairly constant cumulative urinary recovery profile was achieved for longer than 1 month, in which greater than 90% of the dose was administered. The in vitro and in vivo relationship was analyzed and discussed.
Clonidine was applied to the skin of healthy volunteers once weekly by means of a Transdermal Therapeutic System (TTS). The plasma concentration and renal excretion of clonidine, and its effects on mean arterial blood pressure (MAP) and heart rate (HR) were recorded for 7 days, followed by a three-day observation period when a second TTS was applied. Subjective side effects were semiquantitatively recorded. Four different TTS formulations were tested; of which TTS-RP 600679 was the most effective. Following application of this formulation, the plasma level of the drug built-up up during the first 2 days and then remained stable for 120 h at therapeutic concentrations between 0.5 and 0.7 ng/ml; MAP was consistently reduced. During the steady state period the daily urinary clonidine excretion was in the same range as during chronic administration of Catapres tablets 0.15 mg every 12 h, or Catapres Perlongets 0.25 mg every 24 h. Transdermal clonidine applications renewed weekly provide the following therapeutic advantages: 1. patients are protected continuously throughout the entire steady state period; 2. daily fluctuations in plasma clonidine concentration are minimized, which may result in a marked reduction in side effects; and, 3. drug compliance should be improved.