Preparation and Characterization of Tablet Formulation based on Solid Dispersion of Glimepiride and Poly(ester amide) Hyperbranched Polymer

Abstract

The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride and poly(ester amide) hyperbranched polymer into a tablet using a direct-compression tabletting technique was investigated. Tablet cores were additionally coated with hydroxypropyl methylcellulose phthalate in order to protect the extremely hygroscopic solid dispersion from atmospheric moisture. Preliminary stability studies show that glimepiride, which is in amorphous form within solid dispersion, is chemically stable, even if tablets are exposed to elevated temperature and/or moisture. In-vitro dissolution studies show some impact of storage conditions on the tablet cores disintegration time and, consequently, drug release rate. Glimepiride solubility also deteriorates somewhat, most probably due to its partial recrystallization. Storage conditions much less affect the physical stability of coated tablets, which was ascribed to reduced tablet hygroscopicity due to the presence of protecting coating. The hyperbranched polymers are rather new and complex macromolecules. Therefore, we addressed also the biocompatibility of hyperbranched polymer, i.e., its impact on haemolysis of the red blood cells. The concentration required for the haemolytic effect on the red blood cells is around 100-times higher than its expected gastrointestinal luminal concentration, which makes the occurrence of hyperbranched polymer mediated cytotoxicity very unlikely.

Keywords::

• Biocompatibility
• dissolution
• preformulation
• morphology
• solubilization
• stability

Acknowledgments

The authors gratefully acknowledge the financial support of Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Ministry of Higher Education, Science and Technology of the Republic of Slovenia and Slovenian Research Agency.

Declaration of interest

This project was financially supported by Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Ministry of Higher Education, Science and Technology of the Republic of Slovenia and Slovenian Research Agency (research project J2-2078). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.