Details

Autor(en) / Beteiligte

• Benkő, Ernő Máté

Titel

Evaluation of Drug-Matrix Interactions in Directly Compressed Drug Delivery Systems and Modelling of Drug-Release Rate

Ort / Verlag

ProQuest Dissertations Publishing

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Applied Social Sciences Index & Abstracts (ASSIA)

Beschreibungen/Notizen

• Individual differences among patients have considerable importance in the effectiveness of the therapy of different chronic diseases. Co-morbidities, genetical differences or various life-events may cause changes in important physiological parameters affecting the absorption, elimination or effectiveness of drugs and influence treatment efficacy. Personalized medicine is a recently emerging trend (1,2) meant to overcome these difficulties. Therefore, pharmaceutical industry faces a new challenge on providing solid dosage forms, which as still the most favourable medicines, with tailorable properties.Tailored release of drugs has even higher importance in the long-term therapy of chronic diseases, when ensuring a stable plasma level is a key question regarding to the treatment effectiveness. Patient compliance is advised if medicines needed to be administered multiple times throughout long therapies but may be problematic in case of psychiatric or neurodegenerative diseases, or if the administration interval is long, such in case of osteoporosis. Implantable drug delivery devices may provide controlled release for months (3,4), which may be very advantageous in those cases, especially if the active pharmaceutical ingredient (API) has poor bioavailability in the gastrointestinal (GI) tract, such as the antiosteoporotic bisphosphonates.The present work aims the better understanding of the mechanism and kinetics of drug release from directly compressed, biodegradable and non-degradable implantable matrices designed for bisphosphonate delivery, in order to utilize a novel approach on the use of drugpolymer interactions in the tailoring of sustained-release solid delivery matrices.The use of the principles of Quality by Design (QbD) nowadays is essential in applied drug development but its tools such as Design of Experiments (DoE) or artificial neural networks (ANNs) may be well utilized also in fundamental research. In present work they were used to reveal the role of drug-polymer interactions on the Critical Quality Attributes (CQA), such as diametral breaking hardness, porosity and drug dissolution rate of implantable matrices. Therefor a line of chemically similar drugs with increasing acidic strength were formulated in accordance with a mixed 2 and 3 level full factorial DoE. The presence of solid-state drugpolymer interactions based on the formation of H-bonds were confirmed by FT-IR spectroscopy, while their effect on dissolution was estimated by an ANN based predictive model.