Physicochemical Development and Characterization of a Hydroxyapatite-Biocompatible Polymer Matrix for Controlled Insulin Release

Abstract

This study investigates the controlled release of insulin from composite matrices based on hydroxyapatite and Eudragit® polymers, with the aim of developing an efficient and tunable oral or implantable insulin delivery system. Hydroxyapatite was synthesized by chemical precipitation method with a Ca/P molar ratio of 1.66, closely mimicking the stoichiometry of biological apatite, and subsequently thermally treated at 800°C to enhance its crystallinity, mechanical strength, and structural stability. Two distinct matrix formulations were developed using Eudragit® RSPM and Eudragit® RS100, two pH-independent, water-insoluble polymers known for their controlled permeability properties, and were thoroughly characterized in terms of their technological and pharmacotechnical properties. Evaluation demonstrated good matrix cohesion, adequate hardness, and full compliance with mass uniformity requirements according to pharmacopoeial standards. In vitro release studies conducted under physiologically relevant conditions revealed clearly differentiated kinetic profiles depending on both the formulation type and the insulin loading dose. The first batch exhibited a classical first-order release kinetics, achieving complete insulin release over an extended period of seven days, suggesting a diffusion-controlled mechanism. In contrast, the second batch displayed a sigmoidal release profile accurately described by the Boltzmann equation (r² = 0.99), characterized by a marked acceleration phase beginning on the third day, indicative of a more complex release mechanism. These findings demonstrate that insulin loading significantly influences the release mechanism and overall kinetics, highlighting the strong potential of hydroxyapatite-polymer composite matrices for the rational design of advanced controlled insulin delivery systems.