The purpose of this study is to derive an optimal drug release formulation with human clinical bioequivalence in developing a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixed-dose combination (FDC) tablet as a treatment for type 2 diabetes mellitus. As a treatment for type 2 diabetes mellitus, the combined prescription of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is common. Therefore, this study simplified the number of individual drugs taken and improved drug compliance by developing FDC tablets containing sitagliptin phosphate monohydrate as a DPP-4 inhibitor and dapagliflozin propanediol hydrate as an SGLT-2 inhibitor. To derive the optimal dosage form, we prepared single-layer tablets, double-layer tablets, and dry-coated tablets and evaluated the drug control release ability, tableting manufacturability, quality, and stability. Single-layer tablets caused problems with stability and drug dissolution patterns. When the dissolution test was performed on the dry-coated tablets, a corning effect occurred, and the core tablet did not completely disintegrate. However, in the quality evaluation of the double-layer tablets, the hardness was 12–14 kilopond, the friability was 0.2%, and the disintegration was within 3 min. In addition, the stability test revealed that the double-layer tablet was stable for 9 months under room temperature storage conditions and 6 months under accelerated storage conditions. In the drug release test, only the FDC double-layer tablet showed the optimal drug release pattern that satisfied each drug release rate. In addition, the FDC double-layer tablet showed a high dissolution rate of over 80% in the form of immediate-release tablets within 30 min in a pH 6.8 dissolution solution. In the human clinical trial, we co-administered a single dose of a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate FDC double-layered tablet and the reference drug (Forxiga®, Januvia®) in healthy adult volunteers. This study showed clinically equivalent results in the stability and pharmacodynamic characteristics between the two groups.

Background: Sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixeddose combination (FDC) dual-layered tablet is used for type 2 diabetes treatment. Simultaneous quantitative analysis can shorten the analysis time of sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC dual-layered tablets and increase their efficiency. Objective: This study aimed to develop the simultaneous quantitative analysis for sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC dual-layered tablet, a type 2 diabetes treatment. Method: Simultaneous quantitative analysis using the rapid and selective reversed-phase highperformance liquid chromatography (RP-HPLC) method was developed and validated using method validation. RP-HPLC analysis was conducted using an ultraviolent absorption spectrophotometer and a Zorbax C18 column (4.6 x 150 mm, 5 µm). The flow rate and injection volume were set to 1.5 mL min-1 and 20 µL, respectively. The wavelength was set at 205 nm. Results: The retention times of sitagliptin phosphate monohydrate and dapagliflozin propanediol monohydrate were 2.28 mins and 10.65 mins, respectively. The relative standard deviations of the system suitability for validation of simultaneous quantitative analysis were 0.03% for sitagliptin phosphate monohydrate and dapagliflozin propanediol monohydrate. The chromatogram confirmed that there was no peak interference between the two main components and between the main component and the excipients. In addition, It revealed a favorable linearity with correlation coefficients of 0.9999 in the concentration range of 20–120% compared to the standard solution. Conclusion: The developed simultaneous quantitative analysis shortened the analysis time and high efficiency of the sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC bilayer tablet. The validity of the analytical method was verified through accuracy and precision, detection and quantitation limits, and solution stability tests. In addition, it was thought that it would be helpful in developing an analytical method by referring to the simultaneous quantitative analysis method for developing other FDC dual-layered tablets.