IN-VIVO IN-VITRO CORRELATION OF 4 EXTENDED-RELEASE FORMULATIONS OF PSEUDOEPHEDRINE SULFATE/

An in-vivo/in-vitro correlation was established for four formulations of pseudoephedrine sulfate modified release tablets exhibiting differe nt in-vivo and in-vitro release rate and absorption characteristics. I n-vitro release rate data were obtained for 12 individual tablets of e ach formulation using the USP Apparatus 2 paddle stirrer at 50 rev min (-1) in 1000 ml 0.1 N hydrochloric acid for the first hour followed by 0.1 M phosphate buffer at pH 7.5 for hours 2-16. Inspection of the in dividual and mean release rate data indicated that the in-vitro releas e rate of pseudopehedrine sulfate was consistent with the intended des ign of the four extended release formulations. The in-vivo bioavailabi lity and pharmacokinetics of these formulations were evaluated in 20 h ealthy volunteers under fasted conditions. Wagner-Nelson analyses of t he in-vivo data revealed extended release absorption profies for all f our formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in-vitro release resulted in statistica lly significant correlations (r(2) > 0.99, p < 0.0001) for each formul ation. Qualitative rank order correlations were observed among all com binations of in-vivo and in-vitro parameters. These data support a Lev el A correlation between in-vivo absorption profiles and in-vitro rele ase rates of four pseudoephedrine sulfate extended release formulation s determined in fasted healthy volunteers.