Abstract
This study focused on developing a gastroretentive drug delivery system employing a triple-mechanism interpolyelectrolyte complex (IPEC) matrix comprising high density, swelling, and bioadhesiveness for the enhanced site-specific zero-order delivery of levodopa in Parkinson's disease. An IPEC was synthesized and directly compressed into a levodopa-loaded matrix employing pharmaceutical technology and evaluated with respect to its physicochemical and physicomechanical properties and in vitro drug release. The IPEC-based matrix displayed superior mechanical properties in terms of matrix hardness (34-39 N/mm) and matrix resilience (44-47%) when different normality's of solvent and blending ratios were employed. Fourier transform infrared spectroscopy confirmed the formation of the IPEC. The formulations exhibited pH and density dependence with desirable gastro-adhesion with Peak Force of Adhesion ranging between 0.15 and 0.21 N/mm, densities from 1.43 to 1.54 g/cm(3) and swellability values of 177-234%. The IPEC-based gastroretentive matrix was capable of providing site-specific levodopa release with zero-order kinetics corroborated by detailed mathematical and molecular modeling studies. Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery.