Development of a Robust Control Strategy for Fixed-Dose Combination Bilayer Tablets with Integrated Quality by Design, Statistical, and Process Analytical Technology Approach.

Control strategy and quality by design (QbD) are widely used to develop pharmaceutical products and improve drug quality; however, studies on fixed-dose combination (FDC) bilayer tablets are limited. In this study, the bilayer tablet consisted of high-dose metformin HCl in a sustained-release layer and low-dose dapagliflozin l-proline in an immediate-release layer. The formulation and process of each layer were optimized using the QbD approach.

Physicochemical characterization of dapagliflozin and its solid-state behavior in stress stability test.

As an active pharmaceutical ingredient, dapagliflozin propanediol monohydrate (D-PD) has been used in the solvated form consisting of dapagliflozin compounded with (S)-propylene glycol and monohydrate at a 1:1:1 ratio. However, dapagliflozin propanediol loses the solvent's reduced lattice structure at slightly higher temperatures. Due to its sensitive solid-state stability, the temperature and humidity are strictly controlled during the production and storage of dapagliflozin.

Control Strategy for Process Development of High-Shear Wet Granulation and Roller Compaction to Prepare a Combination Drug Using Integrated Quality by Design.

In this study, we developed a control strategy for a drug product prepared by high-shear wet granulation and roller compaction using integrated quality by design (QbD). During the first and second stages, we optimized the process parameters through the design of experiments and identified the intermediate quality attributes (IQAs) and critical quality attributes (CQAs) relationship, respectively. In the first stage, we conducted an initial risk assessment by selecting critical process parameters with high impact on IQAs and CQAs and confirmed the correlation between control and response factors.

Preparation and characterization of metformin hydrochloride controlled-release tablet using fatty acid coated granules.

Metformin hydrochloride (MFM) is often used as a controlled-release (CR) tablet to reduce dosing frequency. However, the MFM CR tablet contains significant amounts of excipients and the tablet size is also large. Dosing convenience and patient compliance can be increased by reducing the size of the CR tablets.

Diastereoselective synthesis of anti-1,2-aminoalcohol by palladium(II) catalyzed aza-Claisen rearrangement.

In this study, a highly diastereoselective synthesis of anti-1,2-aminoalcohol was explored starting from L-amino acids as chiral sources. The higher yield and diastereoselectivity was shown when the aza-Claisen rearrangement was performed with allylic trichloroacetimidate 6a in the presence of palladium(II) catalyst.