Abstract
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® (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® 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® 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 site-specific delivery system.
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