A DESIGN OF EXPERIMENT APPROACH FOR OPTIMIZATION AND CHARACTERIZATION OF ETODOLAC TERNARY SYSTEM USING SPRAY DRYING

摘要

Objective: The objective of the present investigation was to prepare and characterize Etodolac (ETO), Polyvinyl pyrrolidone K30 (PVP K30) and Hydroxypropyl β-cyclodextrin (HPB) ternary system in order to study the effect of complexation on solubility of ETO. Methods: Physical mixtures of a drug and polymers in different weight ratios (1:1, 1:2, 1:4) were prepared to study the effect of individual polymers on solubility of ETO. Spray drying method was used to investigate the combined effect of PVP K30 and HPB on saturation solubility (SS), Dissolution efficiency (DE) and mean dissolution time (MDT) of ETO. Design of experiment (DoE) was used for preparation and optimization of ternary system. Drug polymer interactions were analyzed with Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM), Xray diffraction (XRD) and particle size analysis. Results: Results of solubility study suggested that there was significant increase in solubility of ETO with increase in the concentration of PVP K30, Polyvinyl pyrrolidone K 90 (PVP K90) and HPB (*p<0.05). This might be due to the solubilizing effect of PVP K30, PVPK90 and complex formation of ETO with HPB. Various combinations of PVP K30 and HPB prepared using DoE approach by spray drying method showed greater solubility of ETO than its physical mixtures (*p<0.05). Results of FTIR, DSC, SEM, XRD and particle size analysis revealed the interaction between ETO, PVP K30 and HPB. This suggested formation of amorphous ternary system with mean particle diameter in the range of 763±1.35 nm. Conclusion: Combine use of PVP K30 and HPB with DoE approach was an effective tool for formulating ternary system of ETO.