Optimized copolymeric microstructured platforms for smart controlled delivery of an anticoagulant drug: Preparation, in vitro assessment and crossover study in healthy adult human volunteers

In the present study, novel micro-structured copolymeric carriers were developed based on the grafting technology where acrylamide was chemically crosslinked with different types of Eudragits (R) (NE30D, L100, RL30D, or RS30D) based on a 41*21 factorial design. The designed systems efficiently engulfed the anticoagulant drug dipyridamole (DIP), within their formed entangled mesh of crosslinked polymeric network. An optimized formulation, ECOP4 with a desirability-value of 0.706, (in which DIP is engulfed within a copolymeric network of acrylamide and Eudragit (R) RS30D) showed high engulfment capacity (97.13 +/- 1.34%) and controlled DIP release over 8 h. FTIR studies revealed absence of interactions between DIP and the formed copolymer. ECOP4 was further inserted within an easily-administered safe raft forming system composed of a mixture of LM-pectin and gellan gum. A pharmacokinetic study was performed using human volunteers to determine DIP concentration in their plasma after administering the designed formulation using the high-performance liquid chromatography (HPLC) method. A crossover design was adopted comparing the designed formulation with Persantin (R) 25 mg tablets as a reference standard. Superior results were obtained for the optimized formulation regarding the measured pharmacokinetic parameters (AUC0-24h, Cmax, and Tmax) with a 2.31 fold increase in relative bioavailability, which reveals the usefulness of the designed grafted dipyridamole formulation in sitespecific delivery system.

Automated summary

In this study, novel micro-structured copolymeric carriers were developed using grafting technology to efficiently encapsulate the anticoagulant drug dipyridamole. The optimized formulation ECOP4 showed high encapsulation capacity and controlled release, with a significantly increased relative bioavailability compared to the reference standard Persantin (R) 25 mg tablets. The pharmacokinetic study confirmed the effectiveness of the designed grafted dipyridamole formulation in site-specific delivery.