Correlations between in vitro dissolution rate and bioavailability of alaproclate tablets.
In two different absorption studies, quantitative correlations between the in vitro dissolution rate and the bioavailability have been shown after single administration of various tablet compositions of alaproclate hydrochloride to healthy subjects. Both statistical moment analysis and the use of empirical single value parameters were tested. For conventional tablets a linear relationship was obtained between mean dissolution time in vitro and in vivo. A similar relationship was obtained between the mean dissolution time in vitro and the mean residence time for controlled release tablets of the matrix type. It was also possible to establish an in vitro--in vivo correlation for these latter tablets by using the single point estimate of maximum plasma concentration as in vivo parameter. When comparing the mean dissolution time in vitro to the total area under the plasma drug concentration-time curve attained after different types of tablets, it is obvious that the extent of bioavailability of alaproclate will not fall below 80% of the value found for an aqueous solution until the mean dissolution time in vitro exceeds approximately 3 hr. Statistical moment analysis seems to have a broader applicability than the use of empirical point estimates, and it seems to be useful both for conventionally dissolving tablets and controlled release tablets.
D000042:Absorption; D000328:Adult; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D001682:Biological Availability; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011897:Random Allocation; D012995:Solubility; D013607:Tablets; D013997:Time Factors
D013607:Tablets; C025293:alaproclate; D000409:Alanine