title: Development of a mechanism and an accurate and simple mathematical model for the description of drug release: Application to a relevant example of acetazolamide-controlled release from a bio-inspired elastin-based hydrogel.
abstract: Transversality between mathematical modeling, pharmacology, and materials science is essential in order to achieve controlled-release systems with advanced properties. In this regard, the area of biomaterials provides a platform for the development of depots that are able to achieve controlled release of a drug, whereas pharmacology strives to find new therapeutic molecules and mathematical models have a connecting function, providing a rational understanding by modeling the parameters that influence the release observed. Herein we present a mechanism which, based on reasonable assumptions, explains the experimental data obtained very well. In addition, we have developed a simple and accurate “lumped” kinetics model to correctly fit the experimentally observed drug-release behavior. This lumped model allows us to have simple analytic solutions for the mass and rate of drug release as a function of time without limitations of time or mass of drug released, which represents an important step-forward in the area of in vitro drug delivery when compared to the current state of the art in mathematical modeling. As an example, we applied the mechanism and model to the release data for acetazolamide from a recombinant polymer. Both materials were selected because of a need to develop a suitable ophthalmic formulation for the treatment of glaucoma. The in vitro release model proposed herein provides a valuable predictive tool for ensuring product performance and batch-to-batch reproducibility, thus paving the way for the development of further pharmaceutical devices.
authors.affiliation: Bioforge Research Group, Universidad de Valladolid, CIBER-BBN, Paseo de Belén 19, 47011 Valladolid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Colino
authors.affiliation: Facultad de Ingeniería, Instituto de Investigaciones para la Industria Química (INIQUI-CONICET), Universidad Nacional de Salta, Av. Bolivia 5150, A4408FVY Salta Capital, Argentina. Electronic address: jbermudez@unsa.edu.ar.
authors.forename: J M
authors.initials: JM
authors.lastname: Bermudez
authors.affiliation: Bioforge Research Group, Universidad de Valladolid, CIBER-BBN, Paseo de Belén 19, 47011 Valladolid, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Arias
authors.affiliation: UNITEFA - CONICET, Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000, Córdoba, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Quinteros
authors.affiliation: Facultad de Ingeniería, Instituto de Investigaciones para la Industria Química (INIQUI-CONICET), Universidad Nacional de Salta, Av. Bolivia 5150, A4408FVY Salta Capital, Argentina.
authors.forename: E
authors.initials: E
authors.lastname: Gonzo
mesh_terms: D000086:Acetazolamide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical
chemical_list: D003692:Delayed-Action Preparations; D000086:Acetazolamide
keywords: Biomaterials; Controlled release/delivery; Hydrogels; Mathematical model; Polymeric drug delivery systems