期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 58, 期 -, 页码 34-43出版社
ELSEVIER
DOI: 10.1016/j.ejps.2014.03.001
关键词
Gastroretentive drug delivery; Floating tablets; Drug release simulation; Cellular automata; Release profiles; Dissolution testing
资金
- Omya International AG (Oftringen, Switzerland)
Introduction: Gastroretentive drug delivery systems (GRDDS) play an important role in the delivery of drug substances to the upper part of the gastrointestinal tract; they offer a possibility to overcome the limited gastric residence time of conventional dosage forms. Aims: The aim of the study was to understand drug-release and floatation mechanisms of a floating GRDDS based on functionalized calcium carbonate (FCC). The inherently low apparent density of the excipient (approx. 0.6 g/cm(3)) enabled a mechanism of floatation. The higher specific surface of FCC (approx. 70 m(2)) allowed sufficient hardness of resulting compacts. The floating mechanism of GRDDS was simulated in silico under simulated acidic and neutral conditions, and the results were compared to those obtained in vitro. Methods: United States Pharmacopeia (USP) dissolution methods are of limited usefulness for evaluating floating behavior and drug release of floating dosage forms. Therefore, we developed a custom-built stomach model to simultaneously analyze floating characteristics and drug release. In silico dissolution and floatation profiles of the FCC-based tablet were simulated using a three-dimensional cellular automata-based model. Results: In simulated gastric fluid, the FCC-based tablets showed instant floatation. The compacts stayed afloat during the measurement in 0.1 N FICI and eroded completely while releasing the model drug substance. When water was used as dissolution medium, the tablets had no floating lag time and sank down during the measurement, resulting in a change of release kinetics. Conclusions: Floating dosage forms based on FCC appear promising. It was possible to manufacture floating tablets featuring a density of less than unity and sufficient hardness for further processing. In silico dissolution simulation offered a possibility to understand floating behavior and drug-release mechanism. (C) 2014 Elsevier B.V. All rights reserved.
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