PURPOSE: A method to establish the in vitro-in vivo relationship of oral extended-release products is proposed. METHODS: The approach utilizes incremental amounts of drug released and absorbed within defined time intervals, to construct a chi2 distributed variable for testing in vitro-in vivo similarity. RESULTS: A case study is used to demonstrate that the similarities between incremental values of in vivo absorbed and in vivo dissolved fractions are distinguishable for different dissolution 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 find an optimized dissolution profile to be the surrogate of the in vivo release process of the product.
PURPOSE: A method to establish the in vitro-in vivo relationship of oral extended-release products is proposed. METHODS: The approach utilizes incremental amounts of drug released and absorbed within defined time intervals, to construct a chi2 distributed variable for testing in vitro-in vivo similarity. RESULTS: A case study is used to demonstrate that the similarities between incremental values of in vivo absorbed and in vivo dissolved fractions are distinguishable for different dissolution 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 find an optimized dissolution profile to be the surrogate of the in vivo release process of the product.