Investigations into the relationship between drug properties, filling, and the release of drugs from hard gelatin capsules using multivariate statistical analysis.

PURPOSE

The aim of the present work is to identify complex relationships between formulation variables and dosage form properties to aid the development of hard gelatin capsules.

METHODS

Multivariate statistical analysis was employed based on a statistical design, which considered drug solubility, particle size and concentration, type and concentration of filler and disintegrant, and concentration of standard lubricant and glidant as the main influence factors. Both the filling properties of the formulations and the disintegration/dissolution properties of the capsule content were studied.

RESULTS

From the two multivariate statistical methods used, nonparametric canonical analysis proved to be the superior method to deal with the complex information included in the data. While the filling performance of the formulation could clearly be attributed to the formulation variables such as drug particle size, type of filler, concentration of drug and glidant, the disintegration of the capsules and the dissolution of the drugs was not strongly related to the formulation variables chosen. In this respect as a trend, the drug solubility, and the type of disintegrant and filler appear to be more important factors.

CONCLUSIONS

Based on an appropriate number of experiments, organised in a statistical design, nonparametric canonical analysis can be used to identify relationships in a set of data that is grouped in influence and response variables to aid the development of a dosage form.