European Journal of Biomedical and Pharmaceutical Sciences

DEVELOPMENT AND OPTIMIZATION OF INCLUSION COMPLEXATION OF TERNARY SYSTEM OF CANDESARTAN CILEXETIL USING DESIGN OF EXPERIMENT

Vinchure Bhagyashree D.*, Shaikh Amir A. and Pawar Yogesh D.

ABSTRACT

Background: Now a day some new chemical entities suffer from poor aqueous solubility. The biopharmaceutical classification system (BCS) classifies them as class II substances. Different carriers were used to increase solubility of these class II drugs. Objective:The objective of the present investigation was to study the effect of Physical mixing and High speed homogenization method on drug release of Candesartan (CAND) using polyvinyl pyrrolidone K30 (PVP K30) and β-cyclodextrin (β-CD) to enhance the solubility and bioavailability. Methods: β-CD and PVP K-30 was used to prepare ternary system of Candesartan cilexetil. Central composite design (CCD) was used for preparation and optimization of ternary system. Effect of Physical mixing method and High speed homogenization method was investigated by evaluating Drug release (% R), dissolution efficiency (DE), mean dissolution time (MDT). Characterization of drug and polymer interactions were done using differential scanning calorimetry (DSC), X ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) study. Results: Results of in vitro drug release showed that various combinations of PVP K-30 and β-CD prepared using CCD approach by both the methods showed greater dissolution rate of Candesartan Cilexetil than pure Candesartan Cilexetil (*p< 0.05). Optimized formulation (Run 8) of Physical mixing method and (Run 8) High speed homogenization method gave 67.64% and 92.56% drug release in 60 min, respectively. Results of DSC, XRD and FTIR revealed the interaction of drug with carriers and formation of amorphous ternary system of Candesartan cilexetil. Conclusion: Data obtained by comparing both methods suggest that High speed homogenization method is superior in increasing dissolution of candesartan than physical mixing method. Use of central composite design in preparation of ternary system of Candesartan cilexetil was an effective approach for dissolution enhancement of Candesartan cilexetil.

Keywords: Candesartan cilexetil, Physical mixing method, High speed homogenization method, Polyvinyl pyrrolidone K-30, ?-cyclodextrin, ternary system.