New evaluation method for in vitro/in vivo correlation of enteric-coated multiple unit dosage forms.

PURPOSE

To establish the evaluating method for drug dissolution profiles in the gastrointestinal (GI) tract based on in vitro data for the enteric-coated multiple unit.

METHODS

Dissolution profile in the GI tract was calculated by the convolution procedure using an in vitro dissolution profile as a weighting function, and the gastric-emptying (GE) process as an input function (GE-convolution method). A computer program, GECONV, was developed for numerical execution of the convolution integral.

RESULTS

The in vivo dissolution profile of enteric-coated aspirin granules estimated by GE-convolution was in good agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method using the plasma concentration data after oral administration to healthy subjects. The in vitro/in vivo correlation improved markedly by taking the GE process into consideration.

CONCLUSIONS

These findings indicated that this convolution method is useful for estimating the in vivo dissolution profile of drugs, when they are administered in an enteric-coated multiple unit type dosage form, because the gastric emptying process is a determinant process for the in vivo drug dissolution.