Preparation and in vivo / in vitro Evaluation of a Tri-layer Tablet Containing Glimepiride / Pioglitazone (IR), Metformin (SR) with an Isolation Layer
Taili Zong1,2, Tao Zhang2, Qin He1
1 Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, China, 610041
Correspondence: Qin He, Pharm. D., West China School of Pharmacy, Sichuan University, No. 17, Section 3, Sothern Renmin Road, Chengdu, 610041, China, e-mail: firstname.lastname@example.org.
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 trilayer 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.
Key words Immediate-release layer • In vitro–in vivo correlation • Isolation layer • Sustained-release layer • Tri-layer tablet
pharmind 2011, Nr. 6, Seite 1136