Design of an Interpolyelectrolyte Gastroretentive Matrix for the Site-Specific Zero-Order Delivery of Levodopa in Parkinson’s Disease

Abstract

Abstract. This study focused on developing a gastroretentive drug delivery system employing a triplemechanism 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.

Eudragit E100 and Polysaccharide Polymer Blends as Matrices for Modified-Release Drug Delivery II: Swelling and Release Studies

“…For a cylindrical matric, if n = 0.45, the release mechanism is Fickian diffusion, nonFickian release or anomalous transport if 0.45<n<0.89, case II transport or zero-order release if n = 0.89, and super case II transport if >0.89 [19]. The release exponent n, for all the formulations except LBp displayed non-Fickian release or anomalous transport, indicating that the patterns of release from the matrices were a combination of release mechanisms other than diffusion.…”

Naturapolyceutics: The Science of Utilizing Natural Polymers for Drug Delivery

“…Microbeads fabricated with a blend of alginate and irvingia gum significantly enhanced drug entrapment efficiency and controlled the release of diclofenac sodium over 7 h in comparison to microbeads fabricated with alginate alone [48]. Blends of natural and synthetic gums such as carboxymethyl cellulose/locust bean gum and methacrylate copolymer [49] to produce hydrogels have also been undertaken. Methacrylate copolymer is unsuitable for controlled release formulations, however, its interaction with carboxymethyl cellulose (CMC) produced a hydrogel thereby enhancing the mechanical strength of CMC.…”

“…Increase in concentration implies increase in molecular chains/bonds of the natural polymer available to interact with the mucus. The attachment/mucoadhesion of hakea gum to the mucus (mucin) may be based on non-covalent bondings such as Van der Waals, H-bonding and electrostatic interactions [49]. As the polymer hydrates in the presence of saliva, there is an increase in mobility of the polymer chains producing increased surface for adhesion/interactions with mucin.…”

A Co-blended Locust Bean Gum and Polymethacrylate-NaCMC Matrix to Achieve Zero-Order Release via Hydro-Erosive Modulation

“…It has been shown to exhibit synergistic interactions with other polysaccharides such as xanthan, k-carrageenan, guar gum, and karaya thereby modulating release mechanisms (24,25). It has also been previously demonstrated that a cationic methacrylate copolymer (Eudragit E100) interacts with sodium carboxymethylcellulose (NaCMC) to form an IPEC (26). NaCMC, a traditional hydrogel forming carbohydrate derivative, has a tendency to lose its shape in acidic medium exhibiting a first-order drug release profile.…”

“…Methacrylate copolymer such as Eudragit E100, mainly used as a film-coating agent, was observed to solubilize with ease in an acidic medium and so cannot be used for controlled release delivery. However, a series of studies undertaken in our laboratories indicated that the IPEC formed between the methacrylate copolymer and NaCMC has the potential to form a hydrogel maintaining its three-dimensional shape in acidic medium exhibiting a linear in vitro drug release over 24 h (26)(27)(28)(29). However, it underwent excessive swelling and bulk erosion.…”