Article

Formulation and Evaluation of pH Induced In-situ Nasal Gel of Salbutamol Sulphate

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  • JSPM University's School of Pharmaceutical Sciences
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Abstract

Nasal solutions of Salbutamol Sulphate were prepared for sustaining its release and improving its bioavailability. Carbopol was used as a key ingredient to effect pH induced sol to gel conversion of the formulations. Different formulations were prepared by varying the concentrations of Carbopol 934 and Hydroxyl Propyl Methyl Cellulose. These formulations were evaluated for parameters like pH, drug content, viscosity, gel strength and drug release. Release profile of some formulations showed rapid phase while some showed slow phase. At extreme low concentrations of the polymers, the formulations drained out due to poor viscosity while at higher concentrations of the same the formulations formed stiff gel and showed slow release of drug. Finally optimized formulation with specific concentrations of carbopol 934 and Hydroxyl Propyl Methyl Cellulose showed pH induced sol-gel conversion, sustained release and higher bioavailability.

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... In another beaker add 30 ml of deionized water and mixed with Calcium carbonate, Calcium chloride and stir on magnetic stirrer for 30 min. mixed both the sample and add API and stir for 30 min [16][17][18][19][20][21][22][23][24][25][26][27]. Add required quantity of preservatives. ...
... A mass of 35g is deposited on the lubricated sample. The strength of the gel, which is an index of the viscosity of a gel floating in situ at physiological temperature, was determined by the time in seconds required by weight to penetrate 5 cm into the gel [22][23][24][25][26][27]. ...
... The KBr discs were set up by packing the powders. The samples were scanned between ranges of 400-4000 cm-1 [16,19,23]. ...
... In another beaker add 30 ml of deionized water and mixed with Calcium carbonate, Calcium chloride and stir on magnetic stirrer for 30 min. mixed both the sample and add API and stir for 30 min [16][17][18][19][20][21][22][23][24][25][26][27]. Add required quantity of preservatives. ...
... A mass of 35g is deposited on the lubricated sample. The strength of the gel, which is an index of the viscosity of a gel floating in situ at physiological temperature, was determined by the time in seconds required by weight to penetrate 5 cm into the gel [22][23][24][25][26][27]. ...
... The KBr discs were set up by packing the powders. The samples were scanned between ranges of 400-4000 cm-1 [16,19,23]. ...
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The purpose of this work was to prepare a novel intragastric flotation system for controlled administration of amoxicillin for the treatment of peptic ulcers. By preparing controlled release floating in situ of amoxicillin reduce dosing frequency, better patient compliance , improve bioavailability of drug and minimize side effects. Large doses of amoxicillin (750-1000 mg) can be easily provided in liquid dosage form, which is difficult to integrate into floating tablets. Natural Polymer-based floating gelation system was prepared by dissolving different concentrations of xanthan gum and guar gum in deionized water, then drug (Amoxicillin) and calcium carbonate were added. Fourier transform infrared spectroscopy was used to confirm the presence of interactions between drugs and excipients. 3 2 experimental designs were used for optimization of formulation. The amount of gellan gum (X1) and calcium chloride (X2) were chosen as independent variables. The amount of drug released after 3 hours (Q3) and 6 hours (Q6) and 9 hours (Q9), the viscosity and the floating delay time of the liquid formulation were selected as dependent variables. Floating In-situ gels have been studied for their viscosity, in vitro buoyancy and drug release. The optimized formulation F6 provided sustained in vitro release of drug over an extended period of time up to 12 hrs. The drug release from gel structure follows a zero order release. As per the result and discussion the batch F6 is optimized batch which contain drug release 95.78% up to 12 hr, 67.12% swelling index and show the maximum similarity factor 65.09. FIIR studies showed that there were no interaction between drug and polymer. The stability studies revealed that there were no significant changes in the dependable parameters of the formulation. It is clearly indicates that the optimize formulation were stable for 3 months. In nutshell, we can conclude that the formulated floating in situ gel were successfully formulated for the treatment of the of Peptic Ulcer Disease Caused By Helicobacter pylori.
... Reduction in dose will diminish the side effects and ultimately reduce the treatment cost. While parenteral route is associated with pain at the site of injection, less patient compliance and is inconvenient for longterm therapy [4], the transdermal route on the other hand, though successfully exploited for delivery of certain drugs is limited in its use due to poor permeability of the skin to many drugs [5]. ...
... As anti-asthmatic Salbutamol, Blatta orientalis, sodium cromoglycate, budesonide [4,77,86,89] In diabetes Insulin [17,66,67,97] As anti-emetic Domperidone, metoclopramide hydrochloride, ondansetron [30,68,76] Treatment of malaria Artemether [71] As H 1 anti-histaminic Fexofenadine, dimenhydrinate, pheniramine, chlorpheniramine maleate [72,78,88,92,93] As anti-osteoporotic agent Raloxifene hydrochloride [85] Treatment of epileptic seizures Midazolam hydrochloride [73] As anti-cholinergic Scopolamine hydrobromide [91] In inflammatory condition Ketorolac [95] As uterine stimulant In cardiac disease Oxytocin Metoprolol tartarate [81] [ 75] Other conditions Progesterone, plasmid DNA, Radix bupleuri, vitamin B 12 [34,82,83,87,94] Local activity In allergic condition Mometasone furoate [90] As nasal decongestant Phenylephrine hydrochloride [78] Brain Nasal vaccines Vaccination and immunization H5N1 antigen, adenovirus-based Zaire ebolavirus glycoprotein antigen [60,61] Mucoadhesive in situ nasal gels ...
... Nandgude et al. in 2008 developed in situ nasal gel of salbutamol sulfate using pH-triggered system containing carbopol 934P (0.1 --0.5% w/v) along with viscosity builder and mucoadhesive agent such as HPMC K4M (0.5 --1.5% w/v) which improves and strengthen the gel integrity. The optimized formulation B7 (0.4% w/v carbopol, 1% w/v HPMC K4M) provided sustained in vitro release of drug over an extended period of 48 h which can be a competent alternative to conventional nasal drops [4]. D'Souza et al. formulated insulin nasal gel using carbopol as a gelling agent and evaluated in vitro release and hypoglycemic activity in animal model and healthy human volunteers. ...
Article
Introduction: The nasal route is an attractive target for administration of the drug of choice, particularly in overcoming disadvantages such as high first-pass metabolism and drug degradation in the gastrointestinal environment that are associated with the oral and other modes of administration. The major limitation associated is of rapid mucociliary clearance in the nasal delivery that results in low absorption and hence poor bioavailability. In order to overcome this, mucoadhesive in situ nasal gelling drug delivery systems have been explored to develop sustained/controlled delivery via nasal route. Areas covered: The present review critically evaluates the importance of in situ gel for the nasal delivery of drugs, and the polymers used in the formulation of in situ gel along with their mechanism of gelation. It also encompasses the research reports made in this arena of delivery system. Expert opinion: The challenges of drug delivery through nose has led to development of in situ nasal gelling systems using a myriad of polymers to deliver the drugs, proteins, amino acids, hormones, vaccines and plasmid DNA for the local, systemic and central nervous system effects. Though a range of preclinical reports are available, clinical intricacies need to be critically worked out.
... The formulation was filled aseptically in transparent glass ampoules of 3ml and sterilized by autoclaving at 121°C at 15 psi for 20 min and stored at refrigerator condition. 8,9,10,11 Evaluation of Formulation ...
... The samples were examined for gelation which was said to have occurred when the meniscus would no longer move upon tilting through 90°angle. 8,9,10 ...
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The objective of this work was to formulate and evaluate sustained release epidural injection of analgesic drug diclofenac sodium used in chronic lower back pain. The formulation composed of a thermosensitive polymer Pluronic F127 (20%) and sustained release copolymers HPMC K100M (1%) and HPMC K4M (0.5%) optimized using 32 factorial design. The formulation was found to be clear, colorless, sterile, syringeable through 18gauge, forming a stable gel at 37°C with a gel strength of 9.67g/cm. The drug release was found to be 98.13% in 72 hrs. The formulation was found to be stable at refrigerator temperature of 5°C for a month. Thus, a stable parenteral formulation was developed that can be an appropriate and convenient approach for patients requiring frequent parenteral administration, reducing recurrence of dosage and ultimately expanding patient comfort and satisfaction in case of chronic ailments.
... The in vitro release of plasmid DNA from the gels followed Fickian diffusion. (Nandgude et al., 2008) Carbopol 934 and carbopol 940 are used as a key ingredient to affect pH-induced sol--gel conversion of the formulations for nasal delivery. Shah et al. designed and optimized pHtriggered mucoadhesive in situ nasal gel of sodium cromoglycate using pH-sensitive polymer carbopol 940 and different grades of mucoadhesive polymer HPMC (HPMC K100, HPMC K4M and HPMC K 15M). ...
... The peak plasma concentration was achieved after 45 min of nasal administration of formulation. Nandgude et al. in 2008 developed in situ nasal gel of salbutamol sulfate using pH-triggered system containing carbopol 934P (0.1 -0.5% w/v) along with viscosity builder and mucoadhesive agent such as HPMC K4M (0.5 -1.5% w/v) which improves and strengthen the gel integrity. The optimized formulation B7 (0.4% w/v carbopol, 1% w/v HPMC K4M) provided sustained in vitro release of drug over an extended period of 48 h which can be a competent alternative to conventional nasal drops. ...
Article
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Oral drug delivery is the most desirable, preferred and convenient route for the administration of a drug, whenever systemic effects are intended, However, low oral bioavailability of some actives due to extensive hepatic metabolism and gastrointestinal degradation has prompted the search for more effective routes for their systemic delivery. Transmucosal routes of drug delivery (the mucosal linings of the nasal, rectal, vaginal and buccal cavity), parenteral route and transdermal route offer distinct advantages over peroral administration. These include possible bypass of first-pass effect, avoidance of pre-systemic elimination in gastrointestinal tract (GIT) and hence small dose of a particular drug is required. Reduction in dose will diminish the side effects and ultimately reduce the treatment cost. Intranasal drug delivery can be visualized as the promising route for administration of drugs as it has the potential to overcome some major limitations associated with other listed routes. It is an attractive approach for the systemic delivery of drugs because concentration time profile of drugs achieved after nasal administration is often similar to that obtained after intravenous administration, with resultant rapid onset of pharmacological activity. In addition, intranasal delivery provides a convenient route for the delivery of drugs to central nervous system (CNS) as well as for the products with local activity. Intranasal administration offers several practical advantages from the patient's point of view (rapid onset of action, non invasiveness, essentially painless, ease of delivery, favorable tolerability profile, improved patient compliance, ease of convenience, self-medication) and pharmaceutical industry viewpoint (no need of sterilization of nasal preparations). Copyright © 2018, Mayuri M. Ban et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
... These molecules' random motion causes them to entangle with one another, whether they are manufactured or natural polymers. The interaction between the inorganic and organic colloidal phase units creates the "structural viscosity" that immobilises the liquid continuous phase [2]. As a result, gels have properties halfway between those of liquids and solids. ...
Article
Full-text available
The primary objective of this study is to develop and evaluate phenylephrine nasal gels, aiming for stable blood levels with lower drug doses through consistent administration, avoiding first-pass hepatic metabolism. Compatibility among the drug, polymers, and lipids was confirmed using FTIR and DSC spectra. Phenylephrine nasal gels were formulated, and their clarity assessed. The gels (ONGF1-ONGF8) had pH values of 6.1-7.2, spreadability of 18.33-21.62 g/cm/sec, and viscosity of 934.2-966.2 centipoises. Drug concentration in these formulations varied from 85.52% to 98.88%, indicating acceptable medication content. Gel strength ranged from 64% to 95%. In-vitro drug release of phenylephrine showed 77% to 95% diffusion for ONGF1. The release kinetics followed first order, zero order, Higuchi model, and Korsemeyer-Peppas equations. Kinetic values for all formulations were tabulated. ONGF1 exhibited the most efficient release, with 95% of the drug released within 7 hours, demonstrating a diffusion mechanism followed by non-Fickian transport, adhering to both zero order and Korsemeyer-Peppas models.Top of Form
... The resultant drug mixtures were magnetically stirred for 15 min, and then a phosphate buffer solution was added. Distilled water was used to adjust the final volume to the desired amount [23]. ...
Article
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The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as EDTA (0.2% w/v), sodium taurocholate (0.5% w/v), oleic acid (5% w/v), and Pluronic F 127 (10% w/v), on the nasal absorption of loratadine and chlorpheniramine from in situ nasal gels containing different polymeric combinations, such as hydroxypropyl methylcellulose, Carbopol 934, sodium carboxymethylcellulose, and chitosan, is studied. Among these permeation enhancers, sodium taurocholate, Pluronic F127 and oleic acid produced a noticeable increase in the loratadine in situ nasal gel flux compared with in situ nasal gels without permeation enhancer. However, EDTA increased the flux slightly, and in most cases, the increase was insignificant. However, in the case of chlorpheniramine maleate in situ nasal gels, the permeation enhancer oleic acid only showed a noticeable increase in flux. Sodium taurocholate and oleic acid seems to be a better and efficient enhancer, enhancing the flux > 5-fold compared with in situ nasal gels without permeation enhancer in loratadine in situ nasal gels. Pluronic F127 also showed a better permeation, increasing the effect by >2-fold in loratadine in situ nasal gels. In chlorpheniramine maleate in situ nasal gels with EDTA, sodium taurocholate and Pluronic F127 were equally effective, enhancing chlorpheniramine maleate permeation. Oleic acid has a better effect as permeation enhancer in chlorpheniramine maleate in situ nasal gels and showed a maximum permeation enhancement of >2-fold.
... Temperature sensitive polymers for In -situ gelling system [28][29] There are some polymers which undergo large and unexpected physical and chemical changes in response to small external changes in their environmental conditions. Such polymers are called Stimuli-responsive polymers. ...
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In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behaviour can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. Nasal drug delivery is a better alternative of oral and parental route due to high permeability of Nasal epithelium, rapid drug absorption, avoid Hepatic first pass metabolism, increased bioavailability of drug, minimized local and systemic side effects, Low dose required, Direct transport into systemic circulation and CNS is also possible (passing blood brain barrier), Improved patient compliance, Self-Medication is Possible, prevent Gastro intestinal tract Ulceration. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. Thus, this review focuses on nasal drug delivery, various aspects of nasal anatomy and physiology, nasal absorption mechanism, advantages & disadvantage composition of in situ gel, application and In-situ gels evaluations.
... Emulgel: Using a thermostatic water bath, the oil and water phases were heated independently to 65°c before being combined using a magnetic stirrer. After an emulsion was formed, the prepared gel phase was introduced gradually while being continuously stirred [9]. ...
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Objectives: The benefits of topical drug delivery systems, which have been used for centuries, include the ability to deliver medications both quickly to the affected area where they are most effective and over an extended period of time. These systems lengthen the drug's mean resident time and contact time. The design and characterization of an antibiotic emulgel for topical medication administration is a goal of the current investigation. Methods: Cefpodoxime Proxetil emulgel were prepared using different concentration of Carbopol 934, HPMC K4M and xanthan gum as gelling agents and evaluated the relevant parameters such as physical examinations, pH, extrudability, spreadability, viscosity, swelling index, drug content, in-vitro diffusion studies and microbiology activities. Results: All formulations are neutral and viscosity of emulgel was found in the acceptable limits. On physical evaluations were found to be optimum in terms spreadability, swelling index and extrudability. Drug content of all formulations were found in the ranges 69.73% to 97.58% and CEF4 emulgel exhibiting the highest drug concentration and the lowest percentage drug release due to its controlled release pattern and proven non-fickian diffusion mechanism release. The results found that, the selected formulations proven better bacterial activities against both gram positive and gram negative organisms. Conclusions: Type and concentration of polymers can have an impact on the drug permeability studies and physical-chemical characteristics of the developed antibiotic emulgel, which had excellent results and was suitable for possible therapeutic purposes.
... Visual evaluation of freshly prepared formulations was done to check its clarity, color, odor and general appearance by using standard protocols. 25 Results are shown in Table 4. ...
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Background Nature represents a basic source of medicinal scaffolds that can develop into potent drugs used in the treatment of many diseases. Aim The present study was planned to evaluate the combined effects of polyherbal methanolic extract of the herbs (fruit of capsicum, bark of cinnamon, rhizome of turmeric and rhizome of ginger) that were individually well known for their analgesic and anti-inflammatory activities. Furthermore, we aimed to develop hydrogel formulation of this polyherbal extract and to characterize and evaluate its analgesic and anti-inflammatory potential. Materials and Methods Zingiber officinale (R.), Capsicum annuum (L.), Curcuma longa (L.), and Cinnamomum verum (J.) polyherbal extract (GCTC) was prepared by maceration and evaluated for analgesic and anti-inflammatory potential. Then, two different types of hydrogel formulation were prepared. One is pH-based hydrogel in which carbopol-940 was used and the other is temperature-based gel in which methocel-K100 was used as gelling agent. Different concentrations of polyherbal extract (GCTC), at 1%, 3% and 5%, were used in hydrogel formulation. These prepared hydrogel formulations were characterized and evaluated for analgesic and anti-inflammatory potential. Results Results show that polyherbal extract and all the developed formulations of polyherbal extract (GCTC), at concentrations of 1%, 3% and 5%, have significant analgesic and anti-inflammatory effects with good appearance, homogeneity, spreadability, extrudability and stability. Conclusion It was concluded from this project that polyherbal extract (GCTC) and its hydrogel have significant analgesic and anti-inflammatory potential.
... The prepared microemulgel formulations are visualized for their physical appearance such as color, texture, phase separation, homogeneity and pH [32]. ...
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Topical drug delivery is mostly preferred for dermatological action. Topical dosage form such as cream, ointments, gels etc. has certain drawbacks like stability problems, stickiness, poor absorption as well as permeability. It has limitations in terms of drug solubility, residence time, lipophilicity and permeability. To overcome this, a novel approach microemulsion based gel is formulated. Microemulgel is topical drug delivery system that incorporates the properties of both gel and microemulsion and shows dual release control system. The microemulgel is prepared by reducing the globule size of the emulsion (less than 200nm) so that the drug particles can easily penetrate through stratum corneum. In spite of penetration, microemulgel has several advantages like easily spreadable, non-grease, thixotropic, transparent, and bio-friendly. Currently many drugs of antimicrobial, antifungal and non-steroidal anti-inflammatory class are studied for topical delivery through microemulgel formulation. After the brief study, it can be concluded that the microemulgel appear better and effective delivery system as compared to other topical drug delivery system
... calculated. [16,17] pH measurement pH capacity of the gel was carried out using a digital pH meter by dipping the glass electrode completely into the gel system to cover the electrode. The process of measuring pH was done in triplicate. ...
... Nasal drug delivery has generated widespread interest among the scientific community as an alternative route for the administration of drugs and biomolecules that are also susceptible to enzymatic or acidic degradation and first-pass hepatic metabolism. Nasal delivery seems to be a favorable way to circumvent the obstacles for BBB allowing the direct drug delivery in the biophase of CNS active compounds [9][10][11][12]. Nose to brain route is one of the most permeable and highly vascularized sites for drug administration ensuring rapid absorption and onset of therapeutic action. ...
Article
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Background and Objectives: The aim of present study was to prepare quetiapine fumarate (QF) loaded NE and mucoadhesive NE to enhance the uptake of QF to brain via intranasal (i.n.) delivery. Method: On the basis of solubility studies capmul MCM was selected as the oily phase. The NE was optimized using response surface methodology. A numerical optimization technique was employed to determine the optimal values of variables using desirability approach. Effect of independent variables [(S mix water ratio (X 1), stirring speed (X 2) and stirring time (X 3)] on the dependent variables globule size (Y 1) and in vitro drug release (Y 2) was statistically optimized using 2 3 full factorial design. The optimized batch of NE and mucoadhesive NE was further characterized and evaluated by morphology, zeta sizer, zeta potential, viscosity, pH, transmittance, conductivity, drug content, in vitro release kinetics, ex-vivo permeation and in vivo biodistributionstudies. In order to investigate the localization of QF in brain and nose, qualitatively confocal laser scanning microscopy technique was carried out using coumarin-6 as a marker. Results: Globule size of formulation was antagonistically effected by the independendent variables, whereas the effect was synergistic on the in vitro drug release. The optimal calculated parameters were found to be S mix water ratio (60:25), stirring speed (1000 rpm) and stirring time (15 min). Conclusion: The results of the present investigation showed that QF can be given through intranasal route. This leads to increase in therapeutic effect with lower dose and reducing the side effects by decreasing the drug concentration in other organs. The formulation was free from nasal ciliotoxicity and a more than 14 folds increase in relative bioavailability of QF as compared to oral NE suggested that formulation provides a better mode of systemic delivery of QF.
... Then Carbopol 940 was added slowly to the beaker containing above liquid while stirring. Neutralized the solution by slowly adding triethanolamine solution with constant stirring until the gel is formed21 . ...
... Using what Mann filter paper, the solution was filtered and then 0.1 ml of the filtrate was taken in a beaker and mixed with 10 ml of the alcohol. The content of functional constituent were measured using spectrophotometer at 266 nm (Nandgude et al., 2008). ...
Article
Purpose: To formulate novel topical antifungal gel containing seed extract of c.tora. and to evaluate their antifungal potential. Method: the gel was formulated by a cold mechanical method. Prepared gel was subjected to various evaluation parameters like ph, viscosity, spread ability, homogeneity and antifungal activity. Results: Prepared topical gel of extract was pH range of 6.25±0.05 to 6.45±0.15, viscosity range 386±27.90 to 680±45.50cp, spread ability 40±2.5 to 38±2 mm and homogenous. Prepared topical gel was shown zone of inhibition ranges from 13.5±0.5 to 23.5±0.5 mm for candida albicans. Conclusion: Formulation F6 was shown better antifungal activity as compared to its other formulations. The prepared gel formulation was found useful for topical application due to its neutral pH, good spread ability, low viscosity and no irritation on human skin.
... Visual appearance and clarity were checked under fluorescent light against a white and black back ground for presence of any particulate matter 8 . ...
... The solution was filtered through Whatman filter paper and 0.1 ml of the filtrate was pipetted out and diluted to 10 ml with hexane. The content of active constituents was estimated spectrophotometrically by using standard curve plotted at 470.8 nm [33]. ...
Article
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Objective: The objective of the present investigation was to design and evaluate a gel containing lycopene loaded colloidal microparticles. Methods: The lycopene loaded colloidal microparticles were successfully prepared by Cloud point technique to form colloids using Tween 40 and Tween 60 surfactant solution and then incorporated into microparticles by solvent evaporation method using polymer like HPMC and ethyl cellulose. These colloidal microparticles were evaluated for particle size (PS), drug loading (DL), entrapment efficiency (EE), Scanning Electron Microscopy (SEM). Further, these colloidal microparticles were incorporated into a topical formulation i.e., gel. This topical formulation was then evaluated for macroscopic examination, viscosity, drug content, spreadability, antioxidant activity, in vitro permeation and release kinetics. Results: Colloidal microparticles were successfully prepared and the particle size, drug loading and entrapment efficiency were found to be 249.45±14.2 μm, 49.8±0.96 % and 93.4±0.26 % respectively. FTIR study depicted no chemical interaction between pure drug lycopene and other excipients. The topical formulation showed sustained release and followed Korsmeyer-Peppas release kinetics model. Conclusion: The sustained release topical formulation of lycopene was successfully prepared using Tween 40 and Tween 60 surfactant solution and combination of HPMC and ethyl cellulose and evaluated for several parameters.
... The in vitro gelation of carbopol formulations was evaluated by placing a drop of polymeric solution in vials containing 2 ml of 0.5 M sodium hydroxide which resembles nasal fluid (18), equilibrated at 37°C. The gel formation was assessed visually. ...
Article
Nasal nanovesicular gels of buspirone hydrochloride (BH) were prepared and characterized aiming for sustained delivery and enhancing bioavailability. Buspirone hydrochloride has low bioavailability of about 4% after oral administration due to first pass metabolism. Buspirone hydrochloride nanovesicles were formulated by thin film hydration method (TFH). The selected nanovesicular formulation was incorporated into two types of in situ gels (pH-induced and thermoreversible) using carbopol 974P and poloxamer 407 (P407), respectively, together with different mucoadhesive polymers. The in situ gels were examined for pH, gelling capability, viscosity, content uniformity, mucoadhesiveness, and in vitro drug release. The ex vivo permeation performance of the in situ gel formulations that showed the most sustained release was also assessed. The in vivo study was done by the determination of BH blood level in albino rabbits after nasal administration. Results revealed that nanovesicles prepared using Span 60 and cholesterol in a ratio of 80:20 showed the highest EE% (70.57 ± 1.00%). The ex vivo permeation data confirmed higher permeability figures for carbopol formulation in comparison to poloxamer formulations. The in vivo study data showed an increase of 3.26 times in BH bioavailability when formulated into the carbopol nanovesicular in situ gel relative to control (nasal drug solution).
... At extreme low concentrations of the polymers, the formulations drained out due to poor viscosity while at higher concentrations of the same, the formulations formed stiff gel and showed slowrelease of drug. Finally optimized formulation with specific concentrations of carbopol 934 and hydroxypropyl methylcellulose showed pH induced sol-gel conversion, sustained release and higher bioavailability [88]. ...
Article
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In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the nasal cavity, but once administered, undergo gelation in situ, to form a gel. The formation of gel depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. In the recent years, nasal route has been identified as promising drug delivery route for systemic therapy. Mucoadhesive in situ gel formulations have demonstrated increase in the residence time in the nasal cavity as well enhancement of the permeation characteristics of the drug. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. With a brief introduction to nasal drug delivery, in this paper, the use of novel mucoadhesive in situ gels for the intranasal delivery of drugs is reviewed along with methods available for evaluation of in situ gels.
... The solution was filtered through Whatman filter paper and 0.1 mL of the filtrate was pipetted out and diluted to 10 mL with methanol. The content of active constituents was estimated spectro photometrically by using standard curve plotted at 275 nm (λ max of active constituents in the extracts) (Nandgude et al., 2008). ...
Article
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The objective of the study is to formulate and evaluate a topical herbal gel containing Cardiospermum halicacabum and Vitex negundo leaf extracts for their anti-arthritic activity in rats. Twelve herbal gel formulations were prepared using 1.5% of gelling agents carbopol 934 (F1-F6) and carbopol 940 (F6-F12) and they were evaluated for physical appearance, net content, viscosity, extrudability, pH, spreadability, in vitro diffusion profile and primary skin irritation tests. The stability study for the topical herbal gel formulation was done as per ICH guidelines and anti-arthritic activity was evaluated by Freund’s Complete Adjuvant (FCA) induced arthritis method. Assessment of body weight, paw volume, hematological and biochemical parameters, histopathological examination and In vitro determination of serum biomarkers were also carried out. Formulated gels were homogenous, stable and complied with the guidelines. Among the formulations, F4 showed better release (98.4 %) characteristics than other formulations. No erythema or edema was observed in the skin irritation test confirming the gel was non-toxic and safe. Topical application of the herbal gel F4 containing carbopol 934 displayed significant (p < 0.001) anti-arthritic activity compared to diseased rats. Reduction in paw volume, no agglutination in C - reactive protein and rheumatic factor, reduction in TNFα level, regaining of normal hematological, and biochemical parameters, reduction in spleen and thymus weight and histopathological examination supported the anti-arthritic activity of the gel formulation. © 2016, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved.
... This is a very promising start. However, to judge the final success of a carrier system, the total number of products entering the market in the Table 3: Cosmetic products containing lipid nanoparticles are currently available in the market [38,39] Product name Active ingredients coming years needs also to be considered, the concept of surface modification is further increasing the importance of SLN and NLC among traditional colloidal drug carrier system. SLN and NLC delivery are promising candidates that will enable efficient and targeted delivery of novel drug compound. ...
Article
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Since the beginning of the 1990s the nano-lipid carriers (NLCs) have been attracting a growing interest from the pharmaceutical technology research groups worldwide. NLCs appeared as consumer products first on the cosmetic market. The article gives an overview of the cosmetic benefits including enhancement of chemical stability of actives, film formation, controlled occlusion, skin hydration, skin bioavailability, and physical stability of the lipid nanoparticles. Solid-lipid nanoparticle as topical formulations. List of the cosmetic products currently available in the market, and bioequivalence protocol, excipients, improvement of the benefit/risk ratio of the topical therapy is shown.
... The resultant mixture was stirred for 15 min on a magnetic stirrer and phosphate buffer solution was added. The final volume was made up to the desired quantity with distilled water (14). ...
Article
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The objective of the present work was to formulate and evaluate mucoadhesive in situ nasal gels of loratadine. This drug delivery system may overcome the first-pass metabolism and subsequently improve the bioavailability of the drug. A total of 16 formulations of in situ nasal gels were prepared using different polymeric ratios of hydroxypropyl methylcellulose (HPMC K-100) and xanthan gum. All formulations had a clear appearance in the sol form, with gelling temperature of the nasal gels ranging between 33.1 ± 0.43 and 34.8 ± 0.82 °C. The gelling time of all the formulations varied from 4.0 ± 0.21 to 11.3 ± 0.22 s; the drug content was >95%. The pH of the formulations ranged between 5.6 ± 0.004 and 6.0 ± 0.003, i.e. no mucosal irritation is expected as the pH was in the acceptable range. Mucoadhesive strength was adequate (3010.89 ± 1.21-6678.89 ± 0.45 dyne/cm(2)) to provide prolonged adhesion. In vitro drug release studies showed that the prepared formulations could release the drug for up to 10 h with all of them following Higuchi kinetics. The accelerated stability studies indicated that the gels were stable over the six months test period. The DSC and XRD analysis revealed that there was no drug-polymer interaction. From these findings it can be concluded that in situ nasal gels may be potential drug delivery systems for loratadine to overcome first-pass metabolism and thereby to improve the bioavailability.
... At extreme low concentrations of the polymers, the formulations drained out due to poor viscosity while at higher concentrations of the same, the formulations formed stiff gel and showed slowrelease of drug. Finally optimized formulation with specific concentrations of carbopol 934 and hydroxypropyl methylcellulose showed pH induced sol-gel conversion, sustained release and higher bioavailability [88]. ...
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In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the nasal cavity, but once administered, undergo gelation in situ, to form a gel. The formation of gel depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. In the recent years, nasal route has been identified as promising drug delivery route for systemic therapy. Mucoadhesive in situ gel formulations have demonstrated increase in the residence time in the nasal cavity as well enhancement of the permeation characteristics of the drug. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. With a brief introduction to nasal drug delivery, in this paper, the use of novel mucoadhesive in situ gels for the intranasal delivery of drugs is reviewed along with methods available for evaluation of in situ gels.
... Carbopol 934, an acrylic acid derivative showed in situ gelling by deprotonation at nasal pH. Nandgude et al. formulated pH induced in situ nasal gel of salbutamol sulphate using 0.4-0.5% w/v carbopol 934 for sustained release and enhanced bioavailability whereas chitosan exhibit acidic pH-responsive gelation[43]. Amino groups present on chitosan get protonated towards acidic pH and repulsion between them causes expansion/swelling of the system thus pH dependent gelling[28]. ...
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Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones.
... Pharmacokinetic parameters NEG-9 (SM) marketed tablet with a strength greater than 50 s may be too stiff and cause discomfort (Tanaji et al., 2008). For this reason, the NEGs-1,2,3,4,5,7, and 10 were excluded from further evaluations. ...
... Salbutamol sulphate in-situ gel was formulated with carbopol 934P, HPMC to treat chronic diseases. The optimized formulation containing 0.25% Salbutamol sulphate, 0.4% carbopol, 1% HPMC, 0.9% NaCl, 0.02% benzalkonium chloride, 0.1% sodium metabisulphate showed a sustained drug release for 8 h [45]. ...
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In-situ forming polymeric gelling systems has become prominent among novel drug delivery system (NDDS) in recent years due to advantages such as sustained and prolonged drug action, improved patient compliance and reduced frequency of administration of the drug in comparison to conventional drug delivery system (DDS). This is a type of mucoadhesive DDS where the polymeric formulation is in sol form before administration and once comes in contact with body fluids; it undergoes gelation to form a gel. Use of various natural, biocompatible, biodegradable as well as water soluble polymers such as chitosan, glycoginic acid, poly-caprolactone, gellan gum, xyloglucan, poly-D,L-lactic acid, pluronic F127, carbopol, poly-D, L-lactide-co-glycolide and pectin makes this DDS more acceptable. In-situ gels can be fabricated by various methods in combination with different drugs and polymers for both local and systemic therapy where each drug shows its own therapeutic effects at the targeted site of action. This review presents the current developments and importance of various drugs formulated as in-situ polymeric gelling systems and its corresponding improvement in therapeutic effects.
... At extreme low concentrations of the polymers, the formulations drained out due to poor viscosity while at higher concentrations of the same, the formulations formed stiff gel and showed slowrelease of drug. Finally optimized formulation with specific concentrations of carbopol 934 and hydroxypropyl methylcellulose showed pH induced sol-gel conversion, sustained release and higher bioavailability [88]. ...
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... Evaluation of the gel 2.7.1. Estimation of drug content [12] Each formulation (1 g) containing approximately 40 mg of drug was taken in a 50 mL volumetric flask and diluted with ethanol and shaken to dissolve the drug in ethanol. The solution was filtered through whatmann filter paper; 0.1 mL of the filtrate was pipette out and diluted to 10 mL with ethanol. ...
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Background A novel drug delivery system for treating acute epileptic condition. Objective To develop an intranasal mucoadhesive formulation of Lamotrigine (LTG) loaded insitu gel, for the treatment of epilepsy to avoid possible side effects and first pass metabolism associated with conventional treatment. Methods Lamotrigine was loaded into different polymeric solutions of gellan and xanthan gum. Results All formulations subjected to various evaluation studies were within their acceptable limits. The pH of formulation ranges between 5.8 ±.001 to 6.8 ±.005 indicating that no mucosal irritation is expected as pH was in acceptable range. Invitro drug release from the mucoadhesive insitu gel formulations showed immediate drug release pattern with a maximum drug release of 97.02 ±0.54% for optimized G5 formulation within 20min. Exvivo permeation studies of optimized formulation G5 and control formulation was estimated. Exvivo permeation studies of G5 insitu formulation done for a period of 12 h resulted in slow, sustained release and greater permeability significance(P <0.05) through nasal mucosa when compared to control. Histopathological studies showed that G5 formulation was safer for nasal administration without any irritation. The stability studies indicated that gels were stable over 45 days in refrigerated condition (4±2ºC). Conclusion The intranasal insitu gelling system is a promising novel drug delivery system for an antiepileptic drug lamotrigine which could enhance nasal residence time with increased viscosity and mucoadhesive character and provided better release profile of drug for treating acute epileptic conditions.
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The challenge for efficient drug delivery to patients with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery technologies that can prove their potential to deliver drugs in a controlled, sustained, and targetable manner. Gel technology is one of such emerging technologies, which is no longer limited only to topical applications of drugs and cosmetics for local action. Novel gels prepared by nanotechnology, including vesicular gels, nanogels, emulgels, and so forth, have established their efficacy in terms of drug loading and controlled release of drug from different routes of administration. These novel gels have proven their effectiveness as smart gel systems for drug delivery and other emerging fields. These novel gels have already been employed as drug delivery systems in-vivo and in clinical trials, primarily for cancer therapy, for filling bone defects, acromegaly, periodontal treatment, and many more. This chapter will discuss all the emerging prospects of these novel gels along with their formulation aspects, manufacturing technologies, and current applications.
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The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to pre-corneal elimination of the drug may be overcome by the use of in situ gel forming systems, which upon instillation as drops into the eye undergo a sol-gel transition in the cul-de-sac. This may result in better ocular availability of the drug. The purpose of this work was to develop an ophthalmic delivery system of the NSAID indomethacin, based on the concept of ion activated in situ gelation. Gelrite gellan gum, a novel ophthalmic vehicle, which gels in the presence of mono or divalent cations present in the lacrimal fluid, was used as the gelling agent. The developed formulations were therapeutically efficacious (in a uveitis induced rabbit eye model) and provided sustained release of the drug over an 8-hour period in vitro.