CENTRAL COMPOSITE DESIGN FOR ENHANCEMENT OF ETODOLAC SOLUBILITY VIA INCLUSION COMPLEXATION WITH PVP K-30 AND HYDROXYPROPYL ? –CYCLODEXTRIN

Shaikh Amir A.*, Chaudhari Praveen D. and Lavte Pravind K.

ABSTRACT

Background: Today, 35-40% all 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 co- precipitation and fusion method on drug release of etodolac (ETO) using polyvinyl pyrrolidone K30 (PVP K30) and hydroxypropyl β-cyclodextrin (HPB). Methods: PVP K30 and HPB were used to prepare ternary system of ETO. Central composite design (CCD) was used for preparation and optimization of ternary system. Effect of co-precipitation and fusion method was investigated by evaluating dissolution efficiency (DE), mean dissolution time (MDT) and percent drug release of ETO. Characterization of drug and polymer interactions were done using differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X ray diffraction (XRD) study. Results: Results of in vitro drug release showed that various combinations of PVP K30 and HPB prepared using CCD approach by both the methods showed greater dissolution rate of ETO than pure ETO (*p< 0.05). Optimized formulation (run 3) of co-precipitation and fusion method gave 85.5% and 73% drug release in 10 min, respectively. Results of DSC, SEM and XRD revealed the interaction of drug with carriers and formation of amorphous ternary system of ETO. Conclusion: Data obtained by comparing both methods suggest that co-precipitation method is superior in increasing dissolution of ETO than fusion method. Use of central composite design in preparation of ternary system of ETO was an effective approach for dissolution enhancement of ETO.

Keywords: Etodolac, co-precipitation, fusion method, polyvinyl pyrrolidone K30, hydroxypropyl ?-cyclodextrin, ternary system.