Design of Experiment Centered Multivariate Optimization Strategy for RP-HPLC Method to Quantitate Retapamulin in Topical Cream and Microemulsion

Background: Retapamulin is the first pleuromutilin antibacterial approved for the treatment of impetigo. The objective of the current research was to utilize the design of experiments approach for development and optimization of robust RP-HPLC method for the quantitation of Retapamulin in marketed cream and in-house developed microemulsion based formulations with an oily matrix. Methods: The impact of various chromatographic conditions (independent variables) was assessed using Plackett–Burman design on critical analytical attributes (response) to screen initial experimental conditions. The Box-Behnken design was employed to optimize the selected chromatographic factors on the responses. Further, validation of optimized RP-HPLC was carried out as per the ICHQ2(R1) guideline. Results: Pareto ranking analysis showed that % organic phase, flow rate, and volume of injection were found statistically significant (p < 0.05) variables influencing the retention time, number of plates, and tailing of the Retapamulin peak. The optimized RP-HPLC method with the stationary phase, C18 (250 mm × 4.6 mm, 5 μm) column, and mobile phase as a mixture of methanol and potassium dihydrogen orthophosphate buffer (50 mM, pH 7.0, 90:10 % v/v, isocratic), the flow rate of 1.0 mL/min, 10 μL injection volume, 25°C column oven temperature, 247 nm as detection wavelength, was successfully validated based on ICHQ2(R1) guideline. Conclusion: RP-HPLC method was successfully used to separate (retention time 4.34 ± 0.2 min)and assay Retapamulin in microemulsion and marketed cream. The outcomes of the investigation exhibited the effective application of a multivariant approach in the optimization of the RP-HPLCfor routine analysis of Retapamulin

Improving the Isotretinoin Photostability by Incorporating in Microemulsion Matrix

The present paper demonstrates the increased photostability of isotretinoin when loaded in microemulsion. The photodegradation of isotretinoin, in methanol and microemulsion formulation was studied under direct sun light. The photodegradation process was monitored by UV spectrophotometry. In methanol solution, isotretinoin undergoes complete photodegradation just within a few minutes of light exposure. Isotretinoin incorporated in microemulsion formulation showed an increased stability in comparison to the methanol solutions. In particular for isotretinoin, a residual concentration of 75% was still present after a light irradiance versus a residual value of just 16% measured at the same time in methanol solution. Further, degradation kinetic parameters of isotretinoin-loaded microemulsion formulation were demonstrated increase isotretinoin half-life about five-times in comparison with a methanol solution under a direct sun light

Formulation consideration and characterization of microemulsion drug delivery system for transnasal administration of carbamazepine

The purpose of the present study was to formulate and characterize carbamazepine loaded microemulsion and mucoadhesive microemulsion drug delivery system for its intranasal administration. Carbamazepine microemulsion and mucoadhesive microemulsion were prepared by titration method. The drug-loaded microemulsions were successfully prepared which contain 6% Labrafil M 1944 CS as an oily phase, 32% surfactant mixture of Cremophor RH 40: Transcutol P (4:1) and 62% (wt/wt) aqueous phase. Microemulsion formulation which displayed an optical transparency of 99.95%, globule size of 34.32 ± 1.09 nm, and polydispersity index of 0.127 ± 0.012 was selected for the incorporation of mucoadhesive component. The drug-loaded mucoadhesive microemulsion that contains 0.5% wt/wt of polycarbophil displayed higher in vitro mucoadhesive potential (21.0 ± 3.0 min) and diffusion coefficient (0.3172 ± 0.03) than microemulsion. All formulations were found free from nasal ciliotoxicity and stable for 6 months