Development and Evaluation Op Dissolution Tests using Clinical Data

Abstract

In the present investigation, the in vitro dissolution rates of five commercially available tablets and capsules containing nitrofurantoin were compared with the urinary excretion of the drug and with the calculated dissolution in man. The in vitro dissolution profiles were obtained using the Rotating Basket (USP), the Paddle Method and a Flow-through dissolution cell. No correlation could be found between in vitro and in vivo results using the Rotating Basket or Paddle Methods. With the Flow-through cell, a correlation (r = 0.97) could be shown for only four of the five dosage forms.

A new type of dissolution model has been developed, consisting of two, interconnecting Flow-through cells, in an attempt to enable in vitro/in vivo correlations to be made for all preparations tested. In this novel model, the dosage form disintegrates in the “gastric” part of the model and some of the drug particles are continuously pumped into the “intestinal” part. This new model gave good correlations (r = 0.98) between in vitro and in vivo results for all the tablets and capsules of nitrofurantoin tested.