Macroscopic model to assess the performance of a hydrolytic degrading crosslinked gelatin-poly(vinyl alcohol) hydrogel in the release of an ionically-complexed drug

MARTA B. PEIROTTI; JULIO A. DEIBER; MARIEL L. OTTONE

Los Cocos - Córdoba

Simposio; XII Simposio Argentino de Polímeros - SAP 2017; 2017

Thehydrolytic degradation of a gelatin hydrogel crosslinked with poly(vinylalcohol) and the release of an ionically-complexed enoxaparin in PBS wasmodeled via macroscopic balance equations of species together with kineticequations describing their transformations and transport mechanisms. Simplepseudo-first order kinetic expressions [1] involving network hydrolyticdegradation, network drug detachment, gelatin chain disaggregation, and globaltransport coefficients of free species from the hydrogel to the immersionsolution are proposed and used. The change of average poly(vinyl alcohol)crystal concentration due to dissolution and growth processes is included. Globaltransport coefficients consider the associated interface assumed to be atthermodynamic equilibrium without mass accumulation. From the experimentalvalidation of the model proposed and the discussions of associated phenomena[2], we found that two types of physical situations must be distinguished inrelation to the hydrogel dynamics in vitro. One involves model predictions ofthermodynamic and transport coefficient values for characterization purposes ofthe hydrogel-immersion solution system evolving toward equilibrium. Thus underthis condition a partial drug release is achieved. The other is the use ofthese results to study the dynamic response of the hydrogel when the drugmetabolic rate of species consumption in the immersion solution is differentfrom zero and a total drug release is attained. In this framework, differentdrug release profiles can be determined in relation to the hydrogel span,obtaining time scales of drug persistence and disappearance in both hydrogeland immersion solution at well specified pH, ionic strength and temperature. Itis clear that assessing the performance of a hydrogel drug release system invitro is suitable before further rationalized tests are proposed to decideclinical developments in vivo.