Strategies to improve dissolution and oral absorption of glimepiride tablets: solid dispersion versus micronization techniques.

摘要

The objective of this study is to compare two different dissolution-enhancing strategies, solid dispersion (SD) and micronized techniques, for improving oral absorption of poorly soluble glimepiride, and to decide which strategy is suitable for its solubilization. The formulation of glimepiride SD was prepared by a solvent-evaporation process with povidone k-30 (PVPk30) at a weight ratio of 1:9 (drug:carrier). The other was prepared via a modified micronization technique, where glimepiride was premilled together with lactose and Lutrol F68 until the milled material passes through a 500 mesh ASTM sieve (30 mum). The dissolution results indicated that the two techniques were both capable of enhancing the dissolution rate and extent of glimepiride. The release profiles of the two prepared products were similar to the marketed product (Amaryl(R)) in various types of dissolution media. Furthermore, the oral bioavailability was evaluated for the three formulations in fasted beagle dogs. Statistical analysis indicated that there were no significant differences in pharmacokinetic parameters among the two prepared formulations and a marketed product, especially for AUC, C(max), and T(max). The dissolution parameters (D and AUC) in Tris buffer demonstrated the good in vitro/in vivo relationship with T(max) values for the three formulations. In conclusion, our studies confirmed that both SD and micronization techniques were capable of improving dissolution and oral absorption of glimepiride tablets to a similar extent as the marketed product, and the three glimepiride tablets were bioequivalent in the case of the rate and extent of absorption in dogs.