Mechanistic evaluation of binary effects of magnesium stearate and talc as dissolution retardants at 85% drug loading in an experimental extended-release formulation

被引:31
作者
Durig, T [1 ]
Fassihi, R [1 ]
机构
[1] TEMPLE UNIV,SCH PHARM,DEPT PHARMACEUT SCI,PHILADELPHIA,PA 19140
关键词
D O I
10.1021/js970052v
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The feasibility of producing extended-release matrix tablets with high drug loadings (80-90% w/w) containing a binary combination of magnesium stearate (MS) and talc (T) at different levels as major dissolution retardants was investigated. Matrix tablets were prepared from a granulation containing theophylline, starch, hydroxypropylcellulose, and varying amounts of MS and T. Using a 3(2) factorial design, the effect of MS and T levels on the physical properties and drug release characteristics of the tablets was evaluated. Response surface analysis showed that the binary combination of MS and T at levels >3% adversely affected both tensile strength and friability. A parabolic relationship was observed for the increase in time required for the release of 50% of the theophylline (t(50%)) with increased MS levels. Moreover, as the proportion of MS and T was increased, the release profiles became more linear. A combination of 3% MS and T provided both near zero-order release kinetics as well as a coherent matrix structure. Based on model fitting, a release mechanism combining diffusion and matrix erosion/dissolution is proposed. It may be concluded that in the development of controlled-release systems, the binary combination of MS and T at levels exceeding those conventionally used for lubrication can be employed as an inexpensive, low bulk dissolution retardant for formulations with high drug loading.
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页码:1092 / 1098
页数:7
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