Preparation and in vivo/in vitro Evaluation of a Tri-layer Tablet Containing Glimepiride/Pioglitazone (IR), Metformin (SR) with an Isolation Layer

The objective of the present study was to develop a tri-layer tablet which was administered once daily to improve diabetes patients compliance and achieve better glycemic control. The tri-layer tablet contained glimepiride (CAS number: 93479-97-1) and pioglitazone hydrochloride (CAS number: 112529-15-4) in the immediate-release layer, metformin hydrochloride (CAS number: 1115-70-4) in the sustained-release layer, and an isolation layer between the immediate-release layer and the sustained-release layer to prevent the interaction of the three active components. Pioglitazone hydrochloride was released from the formulation within 15 minutes (immediately). Glimepiride was released from the formulation within 1 hour (moderately). Metformin hydrochloride was released from the formulation within 12 hours (sustainedly). All these composed a once-daily formulation. No significant difference was observed in metformin in vitro release pattern between the tri-layer tablets and the equivalent dose of marketed formulation (metformin hydrochloride SR tablets) (f2 = 66.5). The two preparations were bioequivalent evaluated by a crossover study in six Beagle dogs. Significant sustained-release character was observed in metformin in vivo release of the tri-layer tablet. Moreover, in vitro-in vivo correlation of metformin from the tri-layer tablet was significant.