Abstract
A new controlled-release platform for hydrophilic compounds has been developed, utilizing citric acid-cured epoxidized sucrose soyate (ESS) as the matrix forming material. By cross-linking epoxy groups of ESS with citric acid in the presence of a hydrophilic model molecule, sodium salt of fluorescein (Sod-FS), we were able to entrap the latter homogenously within the ESS matrix. No chemical change of the entrapped active agent was evident during the fabrication process. Hydrophobicity of the matrix was found to be the rate-limiting factor for sustaining the release of the hydrophilic model compound, while inclusion of release-modifiers such as poly(ethylene glycol) (PEG) within the matrix system modulated the rate and extent of guest release. Using 5 kDa PEG at 5% w/w of the total formulation, it was possible to extend the release of the active ingredient for more than a month. In addition, the amount of modifiers in formulations also influenced the mechanical properties of the matrices, including loss and storage modulus. Mechanism of active release from ESS matrices was also evaluated using established kinetic models. Formulations composed entirely of ESS showed a non-Fickian (anomalous) release behavior while Fickian (Case I) transport was the predominant mechanism of active release from ESS systems containing different amount of PEGs. The mean dissolution time (MDT) of the hydrophilic guest molecule from within the ESS matrix was found to be a function of the molecular weight and the amount of PEG included. At the molecular level, we observed no cellular toxicities associated with ESS up to a concentration level of 10 μM. We envision that such fully bio-based matrices can find applications in compounding point-of-care, extended-release formulations of highly water-soluble active agents.
Highlights
Extended-release formulations have been an attractive product platform for therapeutic and diagnostic applications [1]
We report a readily compoundable fabrication process of a hydrophobic matrix system composed of epoxidized sucrose soyate (ESS) that can be used to fabricate extended release delivery formulations of hydrophilic substances in the form of matrices
ESS has a high content of ester linkages within its structure, and curing with bio-based or natural or natural carboxylic acids that cross-link the 3D matrix provides a mechanism for biodegradation of carboxylic acids that cross-link the 3D matrix provides a mechanism for biodegradation of the scaffold the scaffold and the controlled release of any incorporated active molecules
Summary
Extended-release formulations have been an attractive product platform for therapeutic and diagnostic applications [1]. Extending the release of water-soluble guest molecules is an unmet challenge in this area, since many therapeutically active drugs, diagnostic agents, biocides, and fungicides are formulated as the salt of the active molecule to impart maximum engagement with their substrate targets. A set of existing technologies for fabricating extended-release formulations for hydrophilic drugs and bioactive chemical moieties include direct-compression of the active compound into matrices using excipients, micro- and/or nano-encapsulation, or reversible chemical. Polymers 2018, 10, 583 conjugation of the active species with a polymer Among these fabrication processes, polymer-based matrix systems are commonly used for manufacturing extended- and controlled release delivery systems because it makes such manufacturing easy [2]. A matrix-forming polymer, intended for designing extended release formulations of hydrophilic active ingredients, needs to release the entrapped species at a controlled-rate so as to maintain a constant dosage range over an extended period of time. Poly (hydroxy ethylmethacrylate) (PHEMA), poly(vinyl alcohol) (PVA), poly(vinyl pyrrolidone), polyethylene oxide, sodium alginate [3], polyethylene glycol (PEG) [4,5], hydroxypropyl methylcellulose (HPMC) [6,7,8], and hydroxyethyl cellulose (HEC)
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