期刊
JOURNAL OF CONTROLLED RELEASE
卷 99, 期 1, 页码 1-13出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2004.05.011
关键词
polymer blend; plasticizer; coating; release mechanism; aqueous dispersion; pellets
The aim of this study was to investigate the importance of the type of plasticizer in polymer blends used for the coating of solid dosage forms, comparing a lipophilic and a hydrophilic plasticizer (dibutyl sebacate (DBS) and triethyl citrate (TEC)). In vitro drug release from propranolol hydrochloride (propranolol HCl)-loaded pellets coated with blends of ethyl cellulose (EC) and Eudragit(R) L (100:0, 75:25, 50:50, 25:75 and 0: 100 w/w) was investigated at low as well as at high pH. To better understand the underlying mass transport mechanisms, the physicochemical properties of the film coatings (e.g. mechanical resistance, water uptake and dry weight loss behavior) were determined. Interestingly, drug release strongly depended on the type of plasticizer. Importantly, not only the slope but also the shape of the release curves was affected, indicating that the chemical nature of the plasticizer plays a major role for the underlying drug release mechanisms. Diffusion through the intact polymer coatings and/or through water-filled cracks was found to be dominating for the control of drug release. The relative importance of these pathways strongly depended on the polymer blend ratio and type of plasticizer. In contrast to DBS, TEC rapidly leached out of the coatings, resulting in decreasing mechanical resistances of the films and, thus, facilitated crack formation. In addition, the hydrophilicity of the plasticizer significantly affected the water uptake behavior of the film coatings and, hence, changes in the coatings' toughness and drug permeability. Also the relative affinity of the plasticizer to the different polymers was found to be of significance. In contrast to TEC, DBS has a higher affinity to EC than to Eudragit(R) L, resulting in potential redistributions of this plasticizer within the polymeric systems and changes in the release profiles during storage. Importantly, these effects could be avoided with appropriate curing conditions and preparation techniques for the coating dispersions. (C) 2004 Elsevier B.V. All rights reserved.
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