OPTIMIZATION AND USE OF TALC IN DIRECT COMPRESSION TABLET FORMULATIONS

Abstract

Talc is extensively used in a wide variety of cosmetic products, particularly in powder products. Talc keeps the skin feeling smooth and dry. Talc in the pharmaceutical industry is used as a glidant and lubricant. Glidants such as talc improve flow properties of powder by decreasing interparticulate friction, by decreasing van der Waals forces and electrostatic charges, by changing particle size distribution, and by decreasing the effect of humidity on surfaces of host particles by forming a mechanical barrier. The loosely bound lattice layers slide over each other and form roller structures which explains its lubrication characteristics. Talc has less deleterious effect compared to magnesium stearate on tablet in vitro properties. Talcs from different size grades were evaluated for their use in direct compression tablet formulations. Lubricant efficiencies of talcs were measured using ejection force values. The Supra grade of the Cyprus Industrial Mineral company talc was found to be most efficient of the grades tested as lubricant and also gave tablets of more acceptable in vitro properties than tablets lubricated with magnesium stearate only. Additionally talcs in substantial percentages were evaluated for their potential as a direct compression matrix material. With commonly used excipients such as microcrystalline cellulose and lactose, the formulations were self lubricating and the tablets ejected easily. Tablets with very low friability, high crushing strength, rapid dissolution rates, good weight uniformity, content uniformity and potency of drugs were obtained. At similar compression forces, tablet hardness with the 300 grade of Alabama, Altac, and Beaverwhite talcs were significantly greater than corresponding 400 and 500 grades. An optimum direct compression tablet formulation of a conventional theophylline tablet was achieved using the technique of response surface methodology and successive quadratic programming (SQP). The response surfaces were obtained from a second order uniform precision hexagonal design. The tablet formulation was optimized for mean in vitro dissolution time using friability, hardness, ejection force and disintegration time as constraints within the experimental region by the SQP algorithm. The response surface model was validated by preparing and evaluating the predicted formulation. The characteristics of the tablet formulation were analyzed by principal component analysis. Sensitivity analysis of optimal solution was performed for each constraint, while all remaining constraints were held constant. The robustness of the response surface model was evaluated by simulation for error in the compression force values due to its inherent variation. Although pharmaceutical scientists have previously reported optimization studies, the approach