IN-VITRO IN-VIVO RELATIONSHIP OF ORAL EXTENDED-RELEASE DOSAGE FORMS

Purpose. A method to establish the in vitro-in vivo relationship of or al extended-release products is proposed. Methods. The approach utiliz es incremental amounts of drug released and absorbed within defined ti me intervals, to construct a chi(2) distributed variable for testing i n vitro-in vivo similarity. Results. A case study is used to demonstra te that the similarities between incremental values of in vivo absorbe d and in vitro dissolved fractions are distinguishable for different d issolution profiles despite naturally significant linear correlations between cumulative in vivo absorbed and in vitro dissolved fractions ( with different dissolution tests) of an oral extended-release product. Conclusions. The method enables investigators to compare different in vitro dissolution profiles of an oral extended-release product to fin d an optimized dissolution profile to be the surrogate of the in vivo release process of the product.