title: Design of an interpolyelectrolyte gastroretentive matrix for the site-specific zero-order delivery of levodopa in Parkinson's disease.
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.
authors.affiliation: Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
authors.forename: Ndidi C
authors.initials: NC
authors.lastname: Ngwuluka
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000268:Adhesiveness; D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry* / Q000627:therapeutic use; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005685:Galactans / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D006244:Hardness; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007980:Levodopa / Q000737:chemistry* / Q000627:therapeutic use; D008351:Mannans / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010300:Parkinson Disease / Q000188:drug therapy*; D053149:Plant Gums / Q000737:chemistry; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005685:Galactans; D008351:Mannans; D008689:Methacrylates; D053149:Plant Gums; D011108:Polymers; D012997:Solvents; D007980:Levodopa; D002266:Carboxymethylcellulose Sodium; C017471:locust bean gum