Formulation and in vitro/in vivo characterization of a fixed-dose combination tablet of dapagliflozin and rosuvastatin

This study aimed to develop a single fixed-dose combination (FDC) tablet containing dapagliflozin and rosuvastatin, given the increasing use of combined treatment for cardiovascular and chronic kidney diseases, as well as diabetes and dyslipidemia.

Various crystals of dapagliflozin were evaluated for their thermal properties and stability to identify the most stable option. Six different FDC tablets were formulated using excipients determined through compatibility studies, and their dissolution profiles were compared to reference products (Forxiga^® and Crestor^®). Accelerated stability testing and pharmacokinetic studies in beagle dogs were conducted for the selected FDC tablet.

Dapagliflozin citric acid was identified as the most suitable crystal, exhibiting the highest melting point and stability. The manufactured FDC tablets met common compendial properties of solid oral immediate-release tablets. The selected FDC tablet demonstrated comparable dissolution to reference products and superior stability in a 6-month accelerated stability testing. Pharmacokinetic studies confirmed the bioequivalence of the FDC tablet to reference products in beagle dogs.

The developed FDC single tablet of dapagliflozin/rosuvastatin offers a convenient alternative to taking two separate pills and provides insights for developing similar FDC tablets with dapagliflozin or rosuvastatin.