Formulation development of sustained-release hydrophilic matrix tablets of zileuton.
The purpose of this paper was to develop a hydrophilic matrix system for extended oral delivery of zileuton, and study the effects of certain formulation, processing, and dissolution variables on in vitro drug release. Tablet formulations with 60-70% drug and varying release rates were prepared by wet granulation using low and medium viscosity grades of hydroxypropylmethocellulose. In vitro drug release was evaluated using USP apparatus 1. The in vitro drug release from all formulations followed zero-order kinetics and was independent of compression force. In general, the release rate decreased with increasing drug load and higher polymer concentration or viscosity. High-shear granulation also resulted in lower release rate. Accelerated release was observed with increased agitation as well as in the dissolution media with higher surfactant concentration and/or ionic strength. No stereoselective release from the matrix system was observed. The hydrophilic matrix system effectively controlled the in vitro release of zileuton. Matrix tablets with desired release rates can be prepared by adjusting various formulation and processing parameters. The matrix system also has the advantage of simple processing and relatively low cost.
Qiu
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Y
Pharmaceutical and Analytical Research Division, Abbott Laboratories, North Chicago, Illinois 60064-2204, USA. Yihong.Qiu@abbott.com
Hui
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Cheskin
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D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D019245:Compressive Strength; D003692:Delayed-Action Preparations; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016859:Lipoxygenase Inhibitors / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D011108:Polymers; D012399:Rotation; D012995:Solubility; D013501:Surface-Active Agents; D013607:Tablets; D014783:Viscosity; D014867:Water / Q000737:chemistry
D003692:Delayed-Action Preparations; D016859:Lipoxygenase Inhibitors; D011108:Polymers; D013501:Surface-Active Agents; D013607:Tablets; D014867:Water; C063449:zileuton; D006918:Hydroxyurea