THE RATIONAL DEVELOPMENT AND OPTIMIZATION OF CAPSULE FORMULATIONS WITH AN INSTRUMENTED DOSATOR CAPSULE FILLING MACHINE .2. FUNDAMENTALS OF THE OPTIMIZATION STRATEGY

On an instrumented capsule filling machine (Zanasi LZ 64) with intermi ttent operation, the influence of the excipient- and machine parameter s on the filling of the capsules and the dissolution rate using coffei ne as model substance was determined It was found that a sufficient lu brication of the capsule mixture, measurable by low ejection forces, i s critical for a uniform fill weight: Adding too much lubrificant, how ever prevents the compact from forming and the standard deviation of t he fill weight increases. Magnesium stearate and Precirol are more eff ective lubricants than stearic acid. Addition of Aerosil also increase s the fill weight dispersion. The aim of the development should be to compress the mixture with the choice of suitable excipients in a way t hat the small pre-compression forces are sufficient to achieve a trans fer without powder loss. The high porosity of the capsule compact does not allow one to transfer the experience of the disintegration proces s from tablets to capsules. Corn starch delays the disintegration of t he capsules as well as the dissolution rate of the drug substance and is better replaced by lactose 200 mesh or microcrystalline cellulose. A possible optimisation strategy is described