Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.
The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.
Department of Pharmacy and Pharmaceutical Technology, University of Seville, C/Profesor García González 2, 41012, Seville, Spain. mcampinez@us.es.
María Dolores
MD
Campiñez
Department of Pharmacy and Pharmaceutical Technology, University of Seville, C/Profesor García González 2, 41012, Seville, Spain.
Isidoro
I
Caraballo
Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.
Maxim
M
Puchkov
Institute for Pharma Technology, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland.
Martin
M
Kuentz
D001993:Bronchodilator Agents / Q000737:chemistry / Q000493:pharmacokinetics; D003198:Computer Simulation; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011140:Polyurethanes / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013607:Tablets; D013806:Theophylline / Q000737:chemistry / Q000493:pharmacokinetics
D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D011140:Polyurethanes; D013607:Tablets; D013806:Theophylline
controlled release; drug delivery systems; imaging methods; in silico modeling; polyurethanes