A Design of Experiment Approach for Optimization and Characterization of Clarithromycin Ternary System Using Spray Drying

Abstract

The aim of present work was to characterize Clarithromycin (CLT), Polyvinyl pyrrolidone K30 (PVP K30) and Hydroxypropyl β-cyclodextrin (HPB) ternary system so as to check the effect of complexation on solubility of CLT. Physical mixtures of a drug and polymers in several weight ratios (1:1, 1:2) were prepared to check the effect of individual polymers on solubility of CLT. Spray drying method was accustomed investigate the combined effect of PVP K30 and HPB on Drug release (DR), Dissolution efficiency (DE) and mean dissolution time (MDT) of CLT. For the preparation and optimization of ternary system the Design of experiment (DoE) was used . Drug polymer interactions were analyzed with Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD) and particle size analysis. Results of solubility study suggested that there was significant increase in solubility of CLT with increase within the concentration of PVP K30 and HPB (*p<0.05). This may be thanks to the solubilizing effect of PVP K30 and sophisticated formation of CLT with HPB. Various combinations of PVP K30 and HPB prepared using DoE approach by spray drying method showed greater solubility of CLT than its physical mixtures (*p<0.05). Results of FTIR, DSC, XRD and particle size analysis revealed the interaction between CLT, PVP K30 and HPB. This suggested formation of amorphous ternary system with mean particle diameter within the range of 312±1.35 nm. Combine use of PVP K30 and HPB with DoE approach was an efficient tool for formulating ternary system of CLT.
 Keywords: Clarithromycin, Spray drying, polyvinyl pyrrolidone K30, Hydroxypropyl β-cyclodextrin, Design of experiments, Ternary system.