The influence of additives on the presentation of a drug in hard gelatin capsules.

The influence of the concentration of lactose, magnesium stearate and sodium lauryl sulphate in the in vitro dissolution and the drug content of hard gelatin capsules filled under conditions which result in a maximum tapped bulk density, has been evaluated by a factorially-designed experiment. The 3 factors have a significant effect on both drug release and capsule filling. Interactions between the 3 factors, however, limit the exact quantification of the magnitude of their influence by a simple linear model. A quadratic relation, when only 2 factors are considered, can be used to provide a prediction of the influence of these factors. The relations between 2 factors are demonstrated as contours of equal in vitro drug release and equal drug content of capsule, at constant concentrations of the third factor. The contours show the important influence of lactose concentration drug release and capsule filling, and the large changes in response which can occur by the addition of a third factor. They also provide a clear guide to the formulation of hard gelatin capsules.