Formulation of immediate release (Ir) atorvastatin calcium pellets and sustained release (sr) glibenclamide for fixed-dose combination dosage form

Abstract

Objective: The objective of the present research was to develop fixed-dose combinations for the treatment of dyslipidemia, associated with type-II diabetes mellitus for improvement of glucose tolerance. Methods: Multiple unit pellet systems (MUPSs) consisting immediate release atorvastatin calcium pellets and sustained release glibenclamide were formulated by spheronization technique. The characterization of formulated pellets was done by Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) studies, and formulated pellets were evaluated for solubility, viscosity, pH, and in vitro studies. Results: From FT-IR and DSC studies, it was confirmed that no chemical interaction existed between the drug and the natural polymers used. Solubility of glibenclamide was found to be 4.38 and 18.24 and atorvastatin calcium was found to be 6.84, 214.67, and 287.43 g/L. The viscosity of 1% w/v of locust bean gum, guar gum, and ghatti gum was found to be 169 cP, 124 cP, and 31 cP in distilled water. The pH of locust bean gum, guar gum, and gum ghatti solutions was found to be 5.6±0.49, 5.2±0.27, and 4.7±0.51. The in vitro studies suggested that glibenclamide pellets had shown a sustained release till 12 h, while atorvastatin calcium had shown immediate release of drug due to rapid disintegration of pellets. Conclusion: Thus, MUPS can be considered as an alternative approach to treat diabetes induced dyslipidemia.