Design of Experiment Approach to Assess the Effect of Formulation Variables on Extrusion and Spheronization of Telmisartan and Cilostazol Loaded Pellets and its Pharmacokinetic Study

Abstract

Background: Solubility is an important parameter that affects the availability of drug in systemic circulation. Drugs having poor solubility belonging to BCS class II eventually result in lower dissolution and bioavailability. Hence, improvement of solubility is a challenging task. Hence the present work focuses on using solid dispersion and inclusion complex approach for both telmisartan and cilostazol belonging to BCS Class II drugs. Objective: The present study was carried out to improve apparent solubility of telmisartan and cilostazol (BCS-Class II drugs) and optimization as pellets along with its pharmacokinetic study. Methods: Phase solubility study was carried out to screen the excipients such as, PVPK30, PVA, HPMC E5 and β-CD. Solvent evaporation method was adopted to prepare the solid dispersions and inclusion complex of both drugs. Pellets were optimized by extrusion spheronization method using 32 factorial design and characterized by morphology, drug content, DSC, FTIR, XRD, SEM, in- -vitro studies and drug content study. Results: Phase solubility study showed improved apparent solubility of telmisartan with HPMC E5 (1:3) by solid dispersion and cilostazol with β-CD (1:3) using inclusion complexation method. Drug characterization did not reveal any incompatibility. Formulation was optimized on the basis of acceptable pellet properties, including acceptable spherical shape and micromeritics properties. The percent friability of all batches was found to be less than 1%. The optimized pellets of both drugs prepared with micro crystalline cellulose provided desirable maximum release with acceptable release profile. Conclusion: The formulated pellets when studied in vivo showed superior pharmacokinetic profile. The drawback associated with apparent solubility and bioavailability of both drugs can thus be alleviated by use of novel pellet formulation.