Mechanistic evaluation of binary effects of magnesium stearate and talc as dissolution retardants at 85% drug loading in an experimental extended-release formulation.
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 32 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 (t50%) 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.
Dürig
T
T
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
Fassihi
R
R
D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations / Q000737:chemistry*; D019563:Mechanics; D010592:Pharmaceutic Aids / Q000737:chemistry*; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013499:Surface Properties; D013607:Tablets; D013627:Talc / Q000737:chemistry*; D013718:Tensile Strength
D003692:Delayed-Action Preparations; D010592:Pharmaceutic Aids; D013229:Stearic Acids; D013607:Tablets; D013627:Talc; C031183:stearic acid