Modeling in frequency domain used for assessment of in vivo dissolution profile.

PURPOSE

To present a model-dependent approach for the assessment of the in vivo drug dissolution profile based on in vitro data for the multiple unit dosage form, as an alternative to the numerical method proposed in the study by Hayashi et al., Pharm Res. 12:1333-1337 (1995).

METHODS

The data for aspirin granules administered to healthy subjects obtained in the above mentioned study were re-evaluated. The subject dissolution system was considered to consist of two subsystems connected in series, i.e. the subsystem describing the gastric-emptying process and the subsystem describing the intestinal dissolution process. The frequency response method was used to model the subject dissolution system.

RESULTS

The model in vivo dissolution profile of aspirin, assessed as the integral of the model weighting function of the subject dissolution system, was in agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method.

CONCLUSIONS

Comparison of dynamic properties of the subject dissolution system with the subsystem describing the gastric-emptying process yielded quantitative confirmation of the decisive role of the gastric-emptying process in the in vivo drug dissolution after administration in the multi unit dosage form.