Microemulsion-based Gels Research Articles

Evaluation of burn wound healing activity of novel fusidic acid loaded microemulsion based gel in male Wistar albino rats

The objective of the present research was to examine the possible usage of microemulsion based gel for fusidic acid (FA) dermal application as burn wound treatment. During the preparation of microemulsion, ethyl oleate as oil phase, tween 80 as a surfactant, ethanol as co-surfactant, water as aqueous phase were used. The prepared microemulsions were evaluated for clarity, pH, viscosity and FA content. Moreover, stability, sterility, antibacterial activity, in vitro release of the formulations were also evaluated. The results showed that the FA loaded microemulsion and microemulsion based gel formation and characteristics were related to many parameters of the components. The performed optimized microemulsion-based gel showed good stability over a period of 3 months. The antibacterial activity of microemulsion-based gel was found to be comparable with marketed cream. RAW 264.7 macrophages were used to determine cell viability (MTT assay) and nitric oxide production. MBG and FA-MBG significantly inhibit the production of the inflammatory mediator NO in LPS-stimulated RAW 264.7 cells in a concentration-dependent manner. The wound healing property was evaluated by histopathological examination and by measuring the wound contraction. The % of wound area in rats treated with FA (2%) loaded microemulsion based gel ranged from 69.30% to 41.39% in the period from 3 to 10 days. In conclusion, FA loaded microemulsion based gel could be offered as encouraging strategy as dermal systems for the burn wound treatment.

Sucrose-mediated heat-stiffening microemulsion-based gel for enzyme entrapment and catalysis.

Formation of a thermally stiffening microemulsion-based gel showing a nanoconfinement effect of carbohydrates in terms of microviscosity and hydrodynamic diameter of the reverse micelle (specifically with sucrose) is reported. The advantage of this gel as an efficient batch bioreactor for entrapped enzymes (horseradish peroxidase and thermophilic α-glucosidase) was shown, and illustrated its potential biocatalytic application at high temperatures.

Design and study of poloxamer-based microemulsion gels with naproxen

In this study novel microemulsion-based gels with poloxamer 182 as a surfactant were designed and investigated as potential carriers for topical dosage forms with naproxen, non-steroidal anti-inflammatory drug. Based on the analysis of the pseudoternary phase diagrams obtained with the use of different components, oleic acid was selected as an oil phase and ethanol, isopropanol and Transcutol® were used as cosurfactants. As a polar phase pure water and poloxamer 407 solutions were tested. The extent of monophasic areas was similar in both cases, however, the poloxamer solutions were excluded from further experiments because of the lack of gelling properties in the studied systems. As a thickening agent Carbopol® EZ-3 was selected. In three microemulsion systems with different cosurfactans electrical conductivity was analysed as a function of polar phase content in order to find the transition points corresponding to microstructural changes leading to different microemulsion types. In the next step, three bicontinuous systems were transformed into semisolid polymer gels and subjected to rheological and texture profile analyses in order to assess mechanical parameters important in terms of topical drug delivery.

FORMULATION, CHARACTERIZATION, AND IN VITRO EVALUATION OF NOVEL MICROEMULSION-BASED SPRAY FOR TOPICAL DELIVERY OF ISOTRETINOIN

Objective: The present study aimed at the development of a suitable formulation for the treatment of acne using microemulsion-based topical spray system. In this study, we have designed and evaluated novel isotretinoin microemulsion-based spray and gel using basil oil. The rationale of work is to develop single topical formulation with multiple effects by combining effect of retinoid (prevention of comedones formation) and natural oil like basil oil (antibacterial, anti-inflammatory, and penetration enhancer).Methods: The optimized microemulsion-based spray comprised basil oil, Kolliphor RH40, Ethanol, and water was prepared by an aqueous titration method with the help of a ternary phase diagram. The microemulsion-based gel was prepared using Carbopol ETD 2020. The formulations were evaluated for their physicochemical properties. The formulations were subjected to antibacterial activity against Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus using cup plate method against hydrogen peroxide as standard. Finally, the drug released from spray and gel formulations was studied and compared to a commercially available product.Results: Isotretinoin microemulsion-spray showed highest flux (27.67±0.12 μg/cm2/h) in comparison to formulated microemulsion gel (21.81±0.103 μg/cm2/h) and conventional marketed gel (19.29±0.34 μg/cm2/h). The particle size of optimized microemulsion was found to be 68.43 nm. The results indicate that the formulated microemulsion-based spray presents a promising alternative for acne therapy.Conclusion: This mentioned delivery system presented several benefits such as photostability, better patient compliance, antibacterial activity, and good penetration into the desired skin layer when compared to in vitro diffusion of conventional gel and microemulsion-based gel.

Antidermatophytic Activity and Skin Retention of Clotrimazole Microemulsion and Microemulsion-Based Gel in Comparison to Conventional Cream

Aim: Antifungal activity, skin permeation and skin retention of water-in-oil microemulsion (ME) and microemulsion-based gel (MBG) containing clotrimazole (CTZ) were evaluated in comparison to a conventional CTZ cream. Methods: CTZ-ME and CTZ-MBG containing 1% w/w of CTZ were produced. Antifungal activity against Trichophyton mentagrophytes was assessed by the agar diffusion method. Pig skin was used in the in vitro penetration study using modified Franz diffusion cells. Drug amounts which permeated into the receptor fluid, retained in the skin membrane and remained in the donor compartment were analyzed by a validated HPLC technique. Results: CTZ-ME and CTZ-MBG exhibited inhibition zones against T. mentagrophytes whereas the conventional cream did not reveal any inhibition zone in the assay. While no CTZ was detected in the receptor fluid up to 24 h following the in vitro penetration study from all tested formulations, the amount of CTZ retained in the skin membrane when applying CTZ-ME and CTZ-MBG was remarkably higher than that when applying the cream. Conclusion: Results revealed the capacity of ME and MBG in improving skin bioavailability of CTZ while reducing the risk of systemic side effects. Thereby, ME and MBG could increase the efficacy of CTZ for dermatophytosis treatment in comparison to conventional cream.

Assessment of improved buccal permeation and bioavailability of felodipine microemulsion-based cross-linked polycarbophil gel.

The oral bioavailability of felodipine (FEL) is very low, i.e., about 15%. This could be due to low water solubility and hepatic first-pass effect. The objective of the present study was to develop FEL microemulsion-based gel, to bypass the first pass effect, for buccal delivery. The optimized FEL microemulsion (OPT-MEF) was used to prepare buccoadhesive gels, with varying concentrations of hydroxypropyl methylcellulose (HPMC) E4M and polycarbophil (PCP), and evaluated. The cross-linking of the PCP gelling agent was done by adjusting the pH with a neutralizing agent, triethanolamine (TEA). The formulations, namely drug suspension, OPT-MEF, microemulsion-based buccal gel containing 1% w/v (MEF-E4M1), 2% w/v (MEF-E4M2), and 3% w/v (MEF-E4M3) of HPMC K4M and 1% w/v (MEF-PCP1), 2% w/v (MEF-PCP2), and 3% w/v (MEF-PCP3) of PCP were prepared and optimized on the basis of ex vivo permeation study, mucoadhesion force, and viscosity. The optimized buccal gel (MEF-PCP1) showed significantly higher (p < 0.01) permeation flux (J = 0.44 ± 0.16mg/cm2/h), when compared with the drug suspension (J = 0.17 ± 0.14mg/cm2/h). The permeation enhancement ratio of MEF-PCP1 was found to be 2.59 times higher than that of the aqueous suspension of the drug. The texture profile analysis of MEF-PCP1 was performed which showed spreadability (3.2mJ), extrudability (151.8mJ), hardness (13.8g), and adhesiveness (41.0g), and results indicated good spreadability and adhesiveness. The rheological study revealed the pseudoplastic flow behavior of MEF-PCP1 buccal gel. The Cmax value 9.21 ± 2.88μg/ml of MEF-PCP1 gel was found to be significantly higher (P < 0.01) compared to the same dose administered by oral route (Cmax value 3.51 ± 1.74μg/ml). The relative bioavailability (Fr) of the optimized MEF-PCP1 buccal gel was about 397.39% higher than that of oral route. In conclusion, consistent and effective buccal gel containing optimized FEL-loaded microemulsion, with improved buccal permeation and pharmacokinetic parameters was developed successfully to improve the bioavailability of FEL.

Clotrimazole microemulsion and microemulsion-based gel: evaluation of buccal drug delivery and irritancy using chick chorioallantoic membrane as the model.

To investigate the efficacy of clotrimazole microemulsion (CTZ-ME) and its gel form, clotrimazole microemulsion-based gel (CTZ-MBG), for the treatment of oral candidiasis. CTZ-ME and CTZ-MBG were characterized for droplet size and texture, respectively. The ex-vivo permeation study and irritancy assessment of CTZ-ME and CTZ-MBG were performed using chick chorioallantoic membrane (CAM) as the model. Antifungal activity against Candida albicans ATCC 10231 of CTZ-ME and CTZ-MBG was determined by agar diffusion method compared to the blank counterparts. CTZ-ME contained nano-sized droplets and CTZ-MBG had acceptable firmness and spreadability. CTZ-ME exhibited faster CAM permeation of the drug and larger inhibition zone than CTZ-MBG as the increased viscosity of CTZ-MBG resulted in more retardation and higher fluctuations in drug diffusion. As there were no detectable visual changes in CAM blood vessels after applying CTZ-ME or CTZ-MBG, both formulations were non-irritants. CTZ-ME and CTZ-MBG could deliver the drug through CAM, the model for buccal delivery. Additionally, they did not cause irritancy and had effective antifungal activity against C.albicans. The results indicated that CTZ-ME and CTZ-MBG were potential effective antifungal formulations to treat oral candidiasis.

Novel microemulsion-based gels for topical delivery of indomethacin: Formulation, physicochemical properties and in vitro drug release studies

HypothesisMicroemulsion-based semisolid systems may be considered as an interesting alternative to the traditional dosage forms applied in topical drug delivery. Mechanical properties of topical products are important both in terms of application and dosage form effectiveness. In this study we designed and evaluated novel microemulsion-based gels with indomethacin and analyzed the factors affecting their mechanical characteristics and drug release. ExperimentsThe impact of the microemulsion composition on the extent of isotropic region was investigated with the use of pseudoternary phase diagrams. Selected microemulsions were analyzed in terms of electrical conductivity and surface tension in order to determine the microemulsion type. Microemulsions were transformed into polymer-based gels and subjected to rheological and textural studies. Finally, the indomethacin release from the analyzed gels was studied and compared to commercially available product. FindingsThe extent of isotropic domain in pseudoternary phase diagrams seems to be dependent on the polarity of the oil phase. The surface tension and conductivity monitored as a function of water content in microemulsion systems revealed possible structural transformations from w/o through bicontinuous systems into o/w. The mechanical properties of semisolid microemulsion-based systems depended on the composition of surface active agents and the drug presence. The drug release profiles observed in the case of the investigated gels differed from those recorded for the commercially available product which was most probably caused by the different structure of both systems.

Design and Development of Repaglinide Microemulsion Gel for Transdermal Delivery.

Microemulsion formulation of repaglinide, a BCS class II hypoglycemic agent with limited oral bioavailability, was developed considering its solubility in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagrams for microemulsion regions were constructed by water titration method at K m 1:1 and characterized for optical birefringence, percentage transmittance, pH, refractive index, globule size, zeta potential, viscosity, drug content, and thermodynamic stability. To enhance the drug permeation and residence time, the optimized microemulsions having mean globule size of 36.15±9.89nm was gelled with xanthan gum. The developed microemulsion-based gel was characterized for globule size, zeta potential, pH, and drug content. All evaluation parameters upon gelling were found to be satisfactory. Ex vivo permeability study across rat skin demonstrated higher steady-state flux (P<0.05) for microemulsion of repaglinide in comparison to the repaglinide microemulsion gel. At the end of 24h, the cumulative drug permeation from microemulsion and microemulsion gel was found to be 229.19±24.34 and 180.84±17.40μg/cm2, respectively. The microemulsion formulation showed 12.30-fold increase in flux as compared to drug suspension with highest enhancement ratio (E r ) of 12.36. Whereas microemulsion gel exhibited 10.97-fold increase in flux (with highest E r , 11.78) as compared to repaglinide (RPG) suspension. In vivo efficacystudy was performed in normal Sprague-Dawley rats by using oral glucose tolerance test. Results of RPG transdermal microemulsion gel demonstrated remarkable advantage over orally administered RPG by reducing the glucose level in controlled manner. Hence, it could be a new, alternative dosage form for effective therapy of type 2 diabetes mellitus.

Evaluation of a microemulsion-based gel formulation for topical drug delivery of diclofenac sodium

The aim of the current research was to investigate the release of diclofenac sodium, a poorly water-soluble drug from different formulations in vitro. A microemulsion (ME) was prepared using caprylocaproyl polyoxyl-8 glycerides, diethylene glycol monoethyl ether, and propylene glycol monolaurate. For enhancing the viscosity, carbopol was used to form an ME-based gel. The prepared formulations were characterized for physical appearance, droplet size, zeta potential, refractive index, percentage transmittance, heating–cooling cycles, phase separation, pH, conductivity, viscosity, drug content, staining solubility test, transmission electron microscopy and in vitro drug release using Franz diffusion cells. The mean droplets size for ME and ME-based gel-systems were 114.4 ± 0.472, and 178 ± 2.46 nm respectively, whereas the zeta potential values were −33.3 ± 0.64 mV for the former and −33.0 ± 0.40 mV for the latter. No significant variations in the pH nor physical appearance alterations were observed while stability tests were performed. Further, TEM images for drug-loaded ME and the gel exhibited nano-droplets that were spherical in shape. The release rate of diclofenac sodium formulated as ME or as ME gel had the highest release values (76.67 ± 8.63%) and (69.28 ± 7.14%) after 6 h respectively. This was statistically significant (p < 0.0001) compared to the control and different marketed formulations or compounded preparations. The ME-based gel had a higher viscosity suitable for topical administration without dripping. The in vitro result suggested that ME systems are powerful topical vehicles for enhanced penetration of diclofenac sodium.

PREPARATION, CHARACTERIZATION AND ANTIOXIDANT ACTIVITY OF XANTHONE-LOADED MAKING (HODGSONIA HETEROCLITA) MICROEMULSIONS

Objective: The aim of this study was to incorporate xanthone into Making (Hodgsonia heteroclita) microemulsions and to evaluate the antioxidant activity of the formulations.Methods: Making oil was obtained from the seed of Hodgsonia heteroclite by a screw press machine. The solubility of xanthone in various oils, surfactants, and co-surfactants was investigated. Stable Making microemulsion and microemulsion-based gel were simultaneously loaded with xanthone. Finally, an in vitro xanthone release study was carried out and antioxidant activity was determined.Results: The optimal formulations of the Making microemulsion consisted of Making oil, capryol 90, tween 80, propylene glycol, and water. The average droplet size of xanthone-loaded Making microemulsion was around 110–130 nm. It was found that the stability of the xanthone-loaded Making microemulsion-based gel was higher than the xanthone-loaded Making microemulsion. Besides, the release of xanthone from the Making microemulsion-based gel was lower than that of the Making microemulsion. Moreover, it was found that the antioxidant activity of both xanthone-loaded Making microemulsion (TEAC and EC values of 9.8 mmol/mg and 14.8 mmol/mg, respectively) and microemulsion-based gel (TEAC and EC values of 9.4 mmol/mg and 18.5 mmol/mg, respectively) remained high even after extended storage conditions.Conclusion: It was concluded that Making oil is an attractive material to deliver xanthone in pharmaceutical applications.

Transungual Gel of Terbinafine Hydrochloride for the Management of Onychomycosis: Formulation, Optimization, and Evaluation.

The present study was aimed to optimize, develop, and evaluate microemulsion and microemulsion-based gel as a vehicle for transungual drug delivery of terbinafine hydrochloride for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the composition of microemulsion having amount of oil (X 1), Smix (mixture of surfactant and cosurfactant; X 2), and water (X 3) as the independent variables. The formulations were assessed for permeation (micrograms per square centimeter per hour; Y 1), particle size (nanometer; Y 2), and solubility of the drug in the formulation (milligrams per milliliter; Y 3). The microemulsion containing 3.05% oil, 24.98% Smix, and 71.96% water was selected as the optimized formulation. The microemulsion-based gel showed better penetration (∼5 folds) as well as more retention (∼9 fold) in the animal hoof as compared to the commercial cream. The techniques used to screen penetration enhancers (hydration enhancement factor, ATR-FTIR, SEM, and DSC) revealed the synergistic effect of combination of urea and n-acetyl cysteine in disruption of the structure of hoof and hence, leading to enhanced penetration of drug.

Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery.

Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, Smix, and water were confirmed by pseudo-ternary phase diagram studies and central composite design. One percent carbopol 934 was added to form CXB microemulsion-based gel. The final formulation was evaluated for its appearance, pH, viscosity, stability, drug content determination, globule size, and zeta potential. Its ex vivo drug permeation and the in vivo pharmacokinetic was investigated. Further research was performed to ensure the safety and validity by skin irritation study and in vivo anti-inflammatory activity study. Ex vivo permeation study in mice was designed to compare permeation and transdermal ability between microemulsion formulation and conventional gel. The results revealed that optimized microemulsion-based gel gained higher permeation based on smaller globule size and high drug loading of microemulsion. Transdermal ability was also greatly improved. Bioavailability was compared to market Celebrex® by the in vivo pharmacokinetic study in rabbits. The results indicated that CXB microemulsion-based gel had better bioavailability than Celebrex®.

MICROPARTICULATE DRUG DELIVERY SYSTEM FOR TOPICAL ADMINISTRATION OF ITRACONAZOLE

The purpose of the present study was to formulate microemulsion based gel for topical delivery of water insoluble antifungal agent Itraconazole with an aim to increase its penetration through skin and thereby its flux. Pseudoternary phase diagrams were constructed to identify microemulsion existing region using various combinations of surfactant and cosurfactant with oil and water. Solubility of drug in various oils was determined to select the suitable oil having maximum solubilizing capacity for I t raconazole. Different formulations so formed were evaluated for phase separation, isotropic nature, clarity and part icle size analysis and opt imized formulat ions were selected for formulat ing microemulsion based gel using 0.75% w/ w of carbopol 934P NF. The microemulsion-based gels were evaluated for rheological behavior , in- vit ro permeat ion studies and in- vit ro ant ifungal act ivit y. The in- vit ro permeat ion studies was carried out on human cadaver skin, mounted on Keshary-Chien diffusion cell using 10% v/v methanolic solut ion of pH 1.2 phosphate buffer as diffusion medium and Candida albicans as a model fungus to evaluate the ant ifungal act ivity of I t raoconazole through the opt imized formulat ions using cup plate method. Stat ist ically significant increase in in- vit ro permeat ion rate was found among the laboratory microemulsion based gel formulated when compared with convent ional cream formulat ion. The rheological behavior of the prepared systems showed pseudoplast ic ( shear thinning) flow pat tern. The invitro antifungal activity of Itraconazole was found to be significant with microemulsion based gel. Thus it can be concluded that microemulsion based gel is better choice of vehicle for delivery of Itraconazole as topical drug delivery system.

Microemulsions based on paeonol-menthol eutectic mixture for enhanced transdermal delivery: formulation development and in vitro evaluation

In this work, microemulsion-based gels were prepared for transdermal delivery of paeonol. Microemulsions containing eutectic mixtures of paeonol and menthol were developed. The obtained microemulsions were evaluated for particle size, viscosity and physical stability. The selected microemulsions were incorporated into Carbopol gels. Drug crystallization behavior during a short-term storage was compared and in vitro permeation and deposition study were conducted on mouse skin. Results showed that the eutectic liquids of paeonol and menthol at all ratio (6:4, 5:5 and 4:6) could form microemulsions but with significantly different physical characteristics. As the ratio of paeonol increased, the prepared microemulsions exhibited larger droplet size, higher viscosity and quicker crystal growth. Microemulsion containing paeonol and menthol at a ratio of 4:6 possessed the smallest size of 27 nm. Accordingly, the related gel showed better physical stability during 10 days of storage, as well as the highest percent of drug deposition (111.8 μg/cm2) and steady-state flux (0.3 μg/cm2 h). These results suggested that the microemulsion formulation is a preferable approach for enhanced skin permeation, and the microemulsion based on drug–menthol eutectic mixture might be used as a potential transdermal delivery system for better therapeutic efficacy.

Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.

INTRANASAL MICROEMULGEL AS SURROGATE CARRIER TO ENHANCE LOW ORAL BIOAVAILABILITY OF SULPIRIDE

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The purpose of this study is to evaluate microemulsion based gel (MBG) of sulpiride "a poorly water soluble antipsychotic with low oral bioavailability."&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Gelling polymers such as sodium carboxymethylcellulose (CMC-Na), hydroxyl propyl methyl cellulose (HPMC K4m), carbopol 940 and Na alginate were evaluated for their potential to gel sulpiride microemulsions (MEs) without affecting the MEs structure. Also, sulpiride solution (SS) and conventional gel (without ME) were prepared and compared with MBG. Gel formulations were checked for their viscosity, pH, spreadability (S), mucoadhesive force (MF), and nasal ciliotoxicity studies. The &lt;em&gt;in vitro&lt;/em&gt; release of sulpiride across a cellophane membrane and its permeation through the nasal mucosa in phosphate buffered saline pH 6.8 (PBS) were also performed. In addition, a pharmacodynamic study of optimized formulae compared to SS and microemulsion (ME) was evaluated in rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CMC-Na and HPMC K4m were not able to gel sulpiride loaded MEs while Na alginate gave an unclear gel with a sticky texture. Results revealed that the viscosity, mucoadhesion force, and spreadability of the MBG increased with increasing carbopol 940 concentrations. The flux was arranged as the following, MBG&amp;gt;conventional gel&amp;gt;sulpiride solution (SS). According to histopathological study, safe and non-irritant MBGs suitable for nasal administration were successfully prepared. Finally, the pharmacodynamic study indicated that intranasal sulpiride MBG had a significant effect (*P&amp;lt;0.001) than SS and ME administered either intravenous or intranasal.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;MBG provides significant enhancement in nasal bioavailability not only by absorption enhancing effect of ME but also, by increasing nasal residence time&lt;/p&gt;

Microemulsion based Transdermal Gels of Isradipine to Enhance Bioavailability: In vitro and In vivo Evaluation

Aim: The main objective of the current investigation was to develop and evaluate the microemulsion based transdermal gel for isradipine, poorly water soluble and low bioavailable drug. Materials and Methods: Saturation solubility studies of the drug were conducted in various solvents and oils. Oleic acid, Tween 80 and Transcutol P were selected as oil phase, surfactant and cosurfactants, respectively, as the drug was having highest solubility in these solvents. The pseudo-ternary phase diagrams were constructed using water titration method by varying surfactant to the co-surfactant (Smix) ratio as 1:1, 1:2, 1:3, 2:1, and 3:1. Microemulsion formulations ratios were selected from the constructed pseudo-ternary phase diagrams. Results and Discussion: Microemulsion prepared with oil to Smix ratio of 1:9 (F9) was found to be stable with the globule size of 50.4 ± 3.54, and has more % of drug diffusion of 88.4 ± 1.9% within 6 h and has been selected for the preparation of microemulsion based gel (MEBG) using carbopol 934 as gelling agent. The prepared gel has shown 96.74 ± 2.8% drug releases in 8 h which was higher than control gel. In vivo pharmacokinetic studies conducted in rabbits revealed that the bioavailability of MEBG was increased 5.4 times compared to oral suspension. Conclusion: This demonstrates avoidance of first pass metabolism and oral degradation and indicates the effective management of plasma profile of isradipine when it is administered as MEBG through transdermal route.

Preparation, optimization, and evaluation of Zaltoprofen-loaded microemulsion and microemulsion-based gel for transdermal delivery

Context: Zaltoprofen, a non-steroidal anti-inflammatory drug, has potent inhibitory action against nociceptive responses. However, gastrointestinal ulcer accompanied with anemia due to the bleeding are most cited side effects associated with it. Due to this, administration of Zaltoprofen is not suitable for individuals with gastric ulcer. Thus, there is unmet need to develop an alternative delivery system that will be easy to administer and can avoid ulcerogenic side effects associated with it.Objective: Present study was aimed to prepare and evaluate microemulsion (ME) and microemulsion-based gel formulation of Zaltoprofen for transdermal delivery.Materials and methods: Pseudo-ternary phase diagrams were utilized to prepare ME formulations. Effect of surfactant and co-surfactant mass ratio on the ME formation and permeation of ME were evaluated and formulation was optimized. Permeation studies were performed using excised pigskin was studied. Efficacy of optimized formulations was evaluated in rat model of inflammation and pain.Results: Composition of optimized formulation was 1% (w/w) Zaltoprofen, 20% (w/w) Capryol 90, 50% (w/w) Smix (2:1, Cremophor RH 40 and Transcutol P). Optimized formulation showed globule size of 22.11 nm, polydispersity index of 0.251 and zeta potential of –11.4 mV. ME gel was found safe in skin irritation study. Significant analgesic activity and anti-inflammatory activity of ME gel was observed in hot plate test and rat paw edema test, respectively.Conclusion: In conclusion, results of present study suggest that ME could be a promising formulation for transdermal administration of Zaltoprofen.

Microemulsion-based antifungal gel of luliconazole for dermatophyte infections: formulation, characterization and efficacy studies

Luliconazole (LZ), a poorly water soluble synthetic imidazole derivative is used in the treatment of fungal infections of skin. Hence, the investigation was aimed at formulating microemulsion based gels (MBGs) for solubilization of LZ as well as its better penetration for efficacious anti-fungal treatment. The solubility of LZ in various oils was investigated. Out of tried oils, olive oil exhibited highest solubility. Suitable combination of surfactants and co-surfactants were screened for selected oil to yield O/W type microemulsion. The Pseudoternary phase diagrams were developed to determine microemulsion existence area. The developed microemulsion was evaluated for particle size analysis, isotropicity, pH, drug content and rheology. Drug loaded microemulsion was slowly added to the viscous solution of 1 % Carbomer 934 under magnetic stirring to prepare MBG. The prepared MBG were evaluated in terms of their droplet size, spreadability, stability, in vitro permeation studies, and rheological properties. The phase study revealed that the maximum proportion of oil was incorporated in microemulsion systems when the surfactant-to-cosurfactant ratio was 3:1. The microemulsion was optimized with its components of Olive oil as oil, Capmul MCM as a surfactant and iso propyl alcohol as a cosurfactant. The globule size of the optimized batch was 32.59 nm. The MBG was non-irritant indicating their safety and was active against C. albicans indicating its efficacy. Short term stability study performed as per ICH guideline exhibited stable characteristic of developed formulation. Therefore, MBG of LZ is an efficacious treatment for fungal infections.