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Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and
1Department of Pharmaceutical Engineering, Catholic University of Daegu, Hayang-Ro 13-13, Gyeongsan 38430, Republic of Korea.
Pharmaceutics
|April 28, 2023
Summary
A new double-layer tablet combining sitagliptin phosphate monohydrate (a DPP-4 inhibitor) and dapagliflozin propanediol hydrate (an SGLT-2 inhibitor) offers an optimal formulation for type 2 diabetes. Clinical trials confirmed its bioequivalence and stability compared to separate medications.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Clinical Pharmacology
Background:
- Combined therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is common for managing type 2 diabetes mellitus.
- Developing fixed-dose combination (FDC) tablets simplifies medication regimens and improves patient compliance.
Purpose of the Study:
- To develop an optimal fixed-dose combination (FDC) tablet containing sitagliptin phosphate monohydrate and dapagliflozin propanediol hydrate for type 2 diabetes treatment.
- To achieve human clinical bioequivalence for the developed FDC tablet.
Main Methods:
- Prepared and evaluated single-layer, double-layer, and dry-coated tablets for drug release, manufacturability, quality, and stability.
- Conducted dissolution tests, hardness, friability, and disintegration tests.
- Performed human clinical trials comparing the FDC double-layer tablet with reference drugs (Forxiga®, Januvia®).
Main Results:
- Single-layer tablets exhibited stability and dissolution issues; dry-coated tablets showed a "corn-ing" effect.
- The double-layer tablet demonstrated favorable quality (hardness 12-14 kp, friability 0.2%, disintegration <3 min) and stability (9 months room temp, 6 months accelerated).
- The FDC double-layer tablet achieved optimal drug release profiles and >80% dissolution within 30 min at pH 6.8, with clinically equivalent stability and pharmacodynamics in human trials.
Conclusions:
- The sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate FDC double-layer tablet is a stable, manufacturable, and bioequivalent formulation.
- This FDC tablet offers a promising alternative for type 2 diabetes management, enhancing compliance and therapeutic efficacy.
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