Temperature-dependent in Situ Gel of Clotrimazole: an Experimental Study.

BACKGROUND: The in-situ gel-forming polymeric formulations offer sustained and prolonged action in comparison to conventional drug delivery systems. AIM: To formulate and evaluate in situ vaginal gel of clotrimazole. MATERIALS AND METHODS: Poloxamer 407 (20%) was slowly added to freezing water (5°C) with constant stirring. The prepared dispersion was refrigerated for 5 h, the different concentrations of polymers were added for preliminary batches. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were performed for clotrimazole-excipients compatibility study. The final batch was prepared and evaluated for physicochemical parameters, in vitro clotrimazole release, in vitro antifungal activity, and in vivo vaginal tissue irritation test. RESULTS: The compatibility study showed no chemical interaction between clotrimazole and excipients used. The evaluation parameters showed that clotrimazole release was in the range of 8 to 10 h, gelling temperature was in the range of 27-35°C, gelling time was in the range of 28-34 sec, pH was in the range of 4.4-4.8, and viscosities were in the range of 16.4-182.6 cP (solution form) and 10,500-20,756 cP (gel form). The zone of inhibitions for clotrimazole pure drug, the marketed vaginal gel of clotrimazole, and optimized gel formulation was 9.15±0.75 mm, 14.35±1.12 mm, and 18.85±1.56 mm, respectively (p < 0.0001, q = 5.98). An optimized gel formulation was not irritant to vaginal tissue. CONCLUSION: It was possible to formulate effective in situ vaginal gel for control release action of clotrimazole. LEVEL OF EVIDENCE: IIC.

Nuts and Bolts of Oil and Temperature in Topical Preparations of Salicylic Acid.

BACKGROUND: Traditional formulations of salicylic acid in ointment bases have disadvantages of being greasy and irritant due to free crystals. AIM: To explore the method for selection of oils and their ratio for topical preparation on the basis of equilibrium solubility study of salicylic acid and to evaluate temperature effect. MATERIALS AND METHODS: Scanning and calibration curve of salicylic acid in methanol were developed. Among available oils, those that had no interference of absorbance of salicylic acid were short-listed for screening purpose. Selections of oils were carried out on the basis of equilibrium solubility study. Compatibility study was made by Fourier Transform Infra-Red spectroscopy analysis. Primitive study of oil mixtures was done. Selections of the ratio of oils were carried out on basis of constrained simplex-centroid design. RESULTS: Salicylic acid had shown linearity in the range of 15-65 µg/mL in methanol at wavelength maximum (300 nm). From the equilibrium solubility study, Parker Neem® Oil (11.81 ± 0.5 mg/g), Isopropyl Myristate (11.29 ± 0.04 mg/g), Mogra Oil (9.62 ± 0.94 mg/g) were selected. The study possessed the same main Fourier transform infra-red peaks of salicylic acid in the salicylic acid-oils physical mixture. 58.64% Parker Neem® oil and 41.36% isopropyl myristate mixture was selected as optimized batch with the desirability of 0.391. CONCLUSION: The oils mixture could be selected for topical preparation of salicylic acid like paste, cream, ointment etc.

Association of Permeability and Lipid Content of Membrane.

BACKGROUND: Rat skin and goat cul de sac are mostly used in optimization of formulations as the model of human skin and cul de sac. AIM: To explore the correlation between lipid content of rat skin and goat cul de sac and permeability. MATERIALS AND METHODS: Find out wavelength maximum for Sapat plus malam®, Ciplox eye ointment® and chloramphenicol eye caps and the standard curve was also derived. In vitro studies using Cellophane® membrane and ex vivo studies using rat skin or goat cul de sac of the formulations. Permeability coefficient, % dislodgeable dose, lag time, diffusion parameter, and partition coefficient were found for both studies after six and a half hours of penetration studies. Student's unpaired t-test with equal variance was used to find any statistically significant difference in the ex vivo and in vitro diffusion transport studies at 95% level of confidence. RESULTS: Permeability coefficient of Sapat plus malam®, Ciplox eye ointment® and chloramphenicol eye caps were 0.000316 ± 0.0000625, 0.00416 ± 0.0001, 0.0034 ± 0.00004 for Cellophane® membrane and 0.0001 ± 0.000001, 0.002254 ± 0.0002, 0.00303 ± 0.0001 for ex vivo membrane in cm2/min, respectively. For all three formulations, there were calculated t values which were higher than tabulated t values at 95% of confidence level (P<0.05). CONCLUSION: Cellophane® membrane shows a better diffusion than rat skin or goat cul de sac. In the optimization of formulation, only Cellophane® membrane is advisable to use.

Emulsion of Chloramphenicol: an Overwhelming Approach for Ocular Delivery.

BACKGROUND: Ophthalmic formulations of chloramphenicol have poor bioavailability of chloramphenicol in the ocular cavity. AIM: The present study aimed at exploring the impact of different oil mixtures in the form of emulsion on the permeability of chloramphenicol after ocular application. MATERIALS AND METHODS: Selection of oil mixture and ratio of the components was made by an equilibrium solubility method. An emulsifier was chosen according to its emulsification properties. A constrained simplex centroid design was used for the assessment of the emulsion development. Emulsions were evaluated for physicochemical properties; zone of inhibition, in-vitro diffusion and ex-vivo local accumulation of chloramphenicol. Validation of the design using check-point batch and reduced polynomial equations were also developed. Optimization of the emulsion was developed by software Design® expert 6.0.8. Assessment of the osmolarity, ocular irritation, sterility testing and isotonicity of optimized batch were also made. RESULTS: Parker Neem®, olive and peppermint oils were selected as an oil phase in the ratio 63.64:20.2:16.16. PEG-400 was selected as an emulsifier according to a pseudo-ternary phase diagram. Constrained simplex-centroid design was applied in the range of 25-39% water, 55-69% PEG-400, 5-19% optimized oil mixture, and 1% chloramphenicol. Unpaired Student's t-test showed for in-vitro and ex-vivo studies that there was a significant difference between the optimized batch of emulsion and Chloramphenicol eye caps (a commercial product) according to both were equally safe. CONCLUSION: The optimized batch of an emulsion of chloramphenicol was found to be as safe as and more effective than Chloramphenicol eye caps.

Microemulgel of Voriconazole: an Unfathomable Protection to Counter Fungal Contagiousness.

BACKGROUND: Fluconazole and ketoconazole both have poor minimum inhibitory concentration than voriconazole. Voriconazole had serious side effects in oral and intravenous doses. It has poor water solubility. The objective of the study was to prepare and optimize microemulgel of voriconazole for topical delivery. AIM: Formulation, development, and evaluation of voriconazole microemulgel for topical delivery. METHODS: Oil and emulsifi ers selected were on the basis of equilibrium solubility study and emulsification property respectively. The pseudo-ternary plot and constrained simplex lattice design were applied for preparation of microemulsions. Microemulsions were subjected to micelle size, zeta potential, polydispersity index, and in vitro study. They were optimized by Design-Expert® 9.0.3.1 software. Formulation, development, evaluation and optimization of microemulgel were carried out. Microbial assay of an optimized batch of microemulgel was performed. RESULTS: Solubility of voriconazole in Parker Neem® oil was 7.51±0.14 mg/g. Acrysol™K-150: PEG-400 in 4:1 ratio had the highest area for microemulsion. 59.2% Acrysol™K-150, 14.8% PEG-400, 11% Parker Neem® oil, 15% rose water, and 1% voriconazole as an optimized batch of microemulsion was selected for preparation of microemulgel. Carbomer 934P found a good gelling agent in 0-2% w/w concentration. An optimized batch of microemulgel had 0.974 desirability value. An optimized batch of microemulgel and Nizral® cream had 37.32±0.63% and 26.45±0.63% zones of inhibition. CONCLUSION: Topical antifungal treatment was successfully achieved with voriconazole microemulgel.

Microemulgel: an overwhelming approach to improve therapeutic action of drug moiety.

As compared to gel and other topical preparations microemulgel has been prepared by screening of oils, emulsifier, and co-emulsifier on bases of solubility of an API in it. An API has high solubility and oil may also have more or less pharmacological property, so it may assist the therapeutic action of API. Due to presence of oil portion, it leads to more penetration of API in the skin. Oil Micelle Size was less than 500 nm which provides more area for absorption of API in the skin so more penetration and more effective than macro-emulsion. Microemulgel has an advantage of emulgel that has dual benefits of micro-emulsion and gel and several other desirable properties like good consistency, thyrotrophic, greaseless, easily spreadable as well as removable, emollient, non-staining, water soluble, longer shelf-life, bio-friendly, transparent, pleasant appearance, ability of patients for self-medication, termination of medications will be easy, etc.