Effect of microemulsion in topical sertaconazole hydrogel: in vitro and in vivo study.

PURPOSE: A topical microemulsion (ME)-based hydrogel was developed to enhance permeation of an antifungal drug, sertaconazole (STZL) for effective eradication of cutaneous fungal infection. METHODS: Pseudo-ternary phase diagrams were used to determine the existence of MEs region. ME formulations were prepared with oleic acid, Tween 80, propylene glycol (PG) and water. Carbopol 940 (0.75% w/w) was used for preparation of hydrogel of STZL microemulsion (HSM) and characterized. The in vitro and in vivo evaluation of prepared HSM and commercial cream of STZL were compared. RESULTS: The viscosity, average droplet size and pH of HSM were 154.23 ± 0.54 to 162.52 ± 0.21 Pas, 42.3-91.7 nm and 6.9-7.2, respectively. Permeation rate of STZL from optimized formulation (HSM-4), composed with oleic acid (8.75 % w/w), Tween 80 (33.35% w/w), PG (33.35% w/w) and water (24.55% w/w) was observed higher in compare with other HSMs and commercial cream. HSM-4 was stable, three times higher drug retention capacity in skin than commercial cream and did not caused any erythema or edema based on skin sensitivity study on rabbit. The average zone of inhibition of HSM-4 (23.54 ± 0.72 mm) was higher in compare with commercial cream (16.53 ± 0.63 mm) against Candida albicans. CONCLUSION: The results of study showed that ME played a major role in permeation enhancing and skin retention effect of HSM and the concentration of STZL used for cutaneous fungal infection could be decreased by using ME based hydrogel preparation.

Effects of carbohydrate polymers in self-microemulsified tablets on the bioavailability of atorvastatin: In vitro-in vivo study.

AIMS: The concentrations of crospovidone (CP), maltodextrin and microcrystalline cellulose (MCC) have been optimized in the development of self-microemulsified tablets (SMET) to improve the oral bioavailability of an anti-hyperlipidemic drug, atorvastatin, and the in-vivo pharmacokinetic parameters of the optimized SMET were compared with those of a commercial tablet in rabbits. MAIN METHODS: Self microemulsified liquids (SELS) were prepared with oleic acid, Span 40 and Tween 80. SELS were converted into SMET by adsorption, followed by compression using factors such as CP, maltodextrin and MCC, which were optimized through a 2(3)-factorial design considering responses such as the disintegration time and, the times for 50% and 80% of the drug to be released. KEY FINDINGS: The results indicated that CP and MCC were inversely related to the responses, while maltodextrin was directly related to the responses. The droplet size of the disintegrated SMET oil globules was within 2.73 to 4.77 µm. The Cmax and AUC0-∞ of the optimized SMET were found to be 32.5% and 38.8% higher, respectively, than those of the commercial tablet. SIGNIFICANCE: The present results indicate that the bioavailability of the SMET of atorvastatin is better than the commercial formulation.

Microemulsion based topical hydrogel of sertaconazole: formulation, characterization and evaluation.

A microemulsion (ME) based hydrogel had studied as a topical delivery of sertaconazole (STZL) for effective eradication of cutaneous fungal infection. The existence of microemulsion region was investigated in pseudo-ternary phase diagrams and various ME formulations were prepared using oleic acid, Tween 80, propylene glycol and water. Hydrogel of STZL microemulsions (HSM) were prepared in Carbopol 940 (0.75%, w/w) and characterized. The prepared HSM and commercial cream of STZL were evaluated in vitro and ex vivo. The permeation rate of STZL from optimized formulation (HSM-4), composed with oleic acid (8.75%, w/w), tween 80 (33.35%, w/w), propylene glycol (33.35%, w/w) and water (24.55%, w/w) was observed higher in compare with other HSMs and commercial cream. HSM-4 was stable, had 3 times higher drug retention capacity in skin than commercial cream and did not caused any erythema or edema based on skin sensitivity study on rabbit. The average zone of inhibition of HSM-4 (23.54±0.72mm) was higher in compare with commercial cream (16.53±0.63mm) against Candida albicans which may be due to permeation enhancing effect of ME and skin retention effect of HSM. It is promising that the concentration of STZL used to treat cutaneous fungal infection could be decreased due to the high permeation and anti-fungal effect of STZL in HSM-4.

Optimization of HPMC and carbopol concentrations in non-effervescent floating tablet through factorial design.

This study was to optimize HPMC K4M and carbopol 934 concentration in the development of non-effervescent floating tablets (NEFTs) of glipizide as model drug using 3(2) factorial design. The time required for releasing drug of 50% and 80% and similarity factor were the target responses. HPMC K4M and carbopol 934 concentrations were the variables. The response surface methodology and optimized polynomial equations were used to select the optimal formulation with desired responses. The excipients used in tablets were compatible with glipizide as per the results of isothermal stress testing and DSC study. The drug release of entire NEFTs followed zero order kinetics and non-Fickian diffusion mechanism. Validation of the optimization technique demonstrated the reliability of the model. The optimized formulation containing 124.33 mg HPMC K4M and 25.76 mg carbopol 934 was prepared according to the software determined levels. The stability study of the optimized formulation proved the integrity of the developed formulation.

Development and validation of RP-HPLC method for quantification of glipizide in biological macromolecules.

Glipizide (GPZ) has been widely used in the treatment of type-2 diabetics as insulin secretogague. Multiunit chitosan based GPZ floating microspheres was prepared by ionotropic gelation method for gastroretentive delivery using sodiumtripolyphosphate as cross-linking agent. Pharmacokinetic study of microspheres was done in rabbit and plasma samples were analyzed by a newly developed and validated high-performance liquid chromatographic method. Method was developed on Hypersil ODS-18 column using a mobile phase of 10mM phosphate buffer (pH, 3.5) and methanol (25:75, v/v). Elute was monitored at 230 nm with a flow rate of 1 mL/min. Calibration curve was linear over the concentration range of 25.38-2046.45 ng/mL. Retention times of GPZ and internal standard (gliclazide) were 7.32 and 9.02 min respectively. Maximum plasma drug concentration, area under the plasma drug concentration-time curve and elimination half life for GPZ floating microspheres were 2.88±0.29 µg mL(-1), 38.46±2.26 µg h mL(-1) and 13.55±1.36 h respectively. When the fraction of drug dissolved from microspheres in pH 7.4 was plotted against the fraction of drug absorbed, a linear correlation (R(2)=0.991) was obtained in in vitro and in vivo correlation study.

Development and validation of analytical method for the estimation of nateglinide in rabbit plasma.

Nateglinide has been widely used in the treatment of type-2 diabetics as an insulin secretogoga. A reliable, rapid, simple and sensitive reversed-phase high performance liquid chromatography (RP-HPLC) method was developed and validated for determination of nateglinide in rabbit plasma. The method was developed on Hypersil BDSC-18 column (250 mm×4.6 mm, 5 mm) using a mobile phase of 10 mM phosphate buffer (pH 2.5) and acetonitrile (35:65, v/v). The elute was monitored with the UV-vis detector at 210 nm with a flow rate of 1 mL/min. Calibration curve was linear over the concentration range of 25-2000 ng/mL. The retention times of nateglinide and internal standard (gliclazide) were 9.608 min and 11.821 min respectively. The developed RP-HPLC method can be successfully applied to the quantitative pharmacokinetic parameters determination of nateglinide in rabbit model.

Compatibility studies of nateglinide with excipients in immediate release tablets.

Experiments were done to assess the compatibility of nateglinide with selected excipients in the development of immediate release tablets of nateglinide by thermal and isothermal stress testing (IST) techniques. To evaluate the drug-excipient compatibility, different techniques such as differential scanning calorimetric (DSC) study, infra-red (IR) spectrophotometric study and isothermal stress testing were adopted. The results of DSC study showed that magnesium stearate exhibited some interaction with nateglinide. However, the results of IR, and IST studies showed that all the excipients used in the formula were compatible with nateglinide. Optimized formulations developed using the compatible excipients were found to be stable over 3 months of accelerated stability studies (40 ± 2°C and 75 ± 5% RH). Overall, compatibility of excipients with nateglinide was successfully evaluated using a combination of thermal and IST methods and the formulations developed using the compatible excipients were found to be stable.