Stable amorphous binary systems of glipizide and atorvastatin powders with enhanced dissolution profiles: formulation and characterization

Abstract

The aim of this study was to enhance the dissolution profile of the combination of glipizide and atorvastatin used for simultaneous treatment of hyperglycemia and hyperlipidemia. The strategy to formulate coamorphous glipizide–atorvastatin binary mixture was explored to achieve enhancement in dissolution. The coamorphous glipizide–atorvastatin mixtures (1:1, 1:2 and 2:1) were prepared by cryomilling and characterized with respect to their dissolution profiles, preformulation parameters and physical stability. Amorphization was found to be possible by cryomilling at various tried ratios of the two drugs. The data obtained from glass transition temperatures and from Raman spectroscopy point toward practically no interaction between the two drugs. The dissolution studies revealed the highest enhancement in dissolution profiles of cryomilled coamorphous mixtures containing GPZ:ATV in ratios 1:1 (B-5) and 2:1 (B-7). These two mixtures were, therefore, subjected to studies for the evaluation of precompression parameters in order to find their amenability to satisfactory compression into tablet dosage form. The selected formulation was found to be stable when subjected to accelerated stability testing at 40°. C/75% RH for six months as per ICH guidelines. Based on all these studies, it was concluded that GPZ:ATV (1:1) combination may be able to provide an effective therapy for the comorbidities of hyperglycemia and hyperlipidemia.

• Atorvastatin
• cryomilling
• dissolution
• glipizide
• stability studies

Acknowledgements

We are highly thankful to Dr. Lalit M Bhardwaj, Former dean, division of research and development, Lovely Professional University, India, for his continuous and enthusiastic support throughout this study. We also owe our thanks to Dr. Inderpreet Kaur, Scientist, Central Scientific Instruments Organization (CSIO), Chandigarh, India, for helping us to carry out Raman Spectroscopy studies.

Declaration of interest

The authors report no conflicts of interest. The authors are alone are responsible for the content and writing of this article.