Abstract
Objective: Implementation of a new pharmaceutical technique to improve aqueous solubility and thus dissolution, enhancement of drug permeation, and finally formulation of a controlled release tablet loaded with glimepiride (GLMP).
Significance: Improve GLMP bioavailability and pharmacokinetics in type II diabetic patients.
Methods: Different polymers were used to enhance aqueous GLMP solubility of which a saturated polymeric drug solution was prepared and physically adsorbed onto silica. An experimental design was employed to optimize the formulation parameters affecting the preparation of GLMP matrix tablets. A compatibility study was conducted to study components interactions. Scanning electron microscope (SEM) was performed before and after the tablets were placed in the dissolution medium. An in vivo study in human volunteers was performed with the optimized GLMP tablets, which were compared to pure and marketed drug products.
Results: Enhancement of GLMP aqueous solubility, using the polymeric drug solution technique, by more than 6-7 times when compared with the binary system. All the studied formulation factors significantly affected the studied variables. No significant interaction was detected among components. SEM illustrated the surface and inner tablet structure, and confirmed the drug release which was attributed to diffusion mechanism. The volunteer group administered the optimized GLMP tablet exhibited higher drug plasma concentration (147.4ng/mL), longer time to reach maximum plasma concentration (4h) and longer t(1/2) (7.236h) compared to other groups.
Conclusions: Matrix tablet loaded with a physically modified drug form could represent a key solution for drugs with inconsistent dissolution and absorption profiles.