Romi Barat Singh

Systematic Development and Optimization of an in-situ Gelling System for Moxifloxacin Ocular Nanosuspension using High-pressure Homogenization with an Improved Encapsulation Efficiency

BACKGROUNDnThe objective of this study was to apply Quality by Design (QbD) principles on process parameter optimization for the development of hybrid delivery system (combination of (SLNs) and In-situ gelling system) for hydrophilic drug Moxifloxacin Hydrochloride (MOX) to achieve its controlled delivery, which otherwise may not be possible through single type of technology.nnnMETHODSnRisk assessment studies were carried out to identify probable risks influencing CQAs on the product. In design of experiments (DoE), the process parameters (independent variables) i.e., chiller temperature X1, High Pressure Homogenization (HPH) pressure X2, and HPH cycles X3 were optimized using a three-factor two level face-centered central composite design to streamline the influence on three responses, namely encapsulation efficiency Y1, particle size Y2 and outlet temperature Y3. Independent and dependent variables were analyzed to establish a full-model second-order polynomial equation. F value is used to confirm the omission of insignificant parameters/interactions to derive a reduced-model polynomial equation to predict the Y1, Y2 and Y3 for optimized moxifloxacin in situ gelled nanosuspension.nnnRESULTSnDesirability plots showed the effects of X1, X2, and X3 on Y1, Y2 and Y3, respectively. The design space is generated to obtain optimized process parameters viz. chiller temperature (-5°C), HPH pressure 800 - 900 bar and 8 cycles that resulted in nanosuspension with ≈ 500 nm size, encapsulation efficiency >65% and final formulation temperature <23°C that were necessary to maintain the formulation in a liquid state.nnnCONCLUSIONnQuality by Design (QbD) approach is recently been encouraged by regulatory bodies to improve the quality of the finished product. This approach proved to be a useful tool in the development of robust nanosuspension of highly hydrophilic drugs with improved efficiency. Results indicate that such hybrid gel systems can be used to control the release of SLNs from application site and prolong their action in a sustained manner.

Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir

Objective The aim of the present study was to improve bioavailability of an important antiretroviral drug, Darunavir (DRV), which has low water solubility and poor intestinal absorption through solid dispersion (SD) approach incorporating polymer with P-glycoprotein inhibitory potential. Methods A statistical approach where design of experiment (DoE) was used to prepare SD of DRV with incorporation of P-glycoprotein inhibitors. Using DoE, different methods of preparation, like melt, solvent evaporation, and spray drying method, utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. The optimized SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for enhancement in absorption using everted gut sac model, effect of food on absorption of DRV, and in vivo prospect. Results and Discussion DSC, FTIR, XRD, and SEM confirmed the amorphicity of drug in SD. Oral bioavailability studies revealed better absorption of DRV when given with food. Absorption studies and in vivo study findings demonstrated great potential of Kolliphor TPGS as P-glycoprotein inhibitor for increasing intestinal absorption and thus bioavailability of DRV. Conclusion It is concluded that SD of DRV with the incorporation of Kolliphor TPGS was potential and promising approach in increasing bioavailability of DRV as well as minimizing its extrusion via P-glycoprotein efflux transporters.