In-vivo/in-vitro correlation of four extended release formulations of pseudoephedrine sulfate.
An in-vivo/in-vitro correlation was established for four formulations of pseudoephedrine sulfate modified release tablets exhibiting different in-vivo and in-vitro release rate and absorption characteristics. In-vitro release rate data were obtained for 12 individual tablets of each 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 individual and mean release rate data indicated that the in-vitro release rate of pseudoephedrine sulfate was consistent with the intended design of the four extended release formulations. The in-vivo bioavailability and pharmacokinetics of these formulations were evaluated in 20 healthy volunteers under fasted conditions. Wagner-Nelson analyses of the in-vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in-vitro release resulted in statistically significant correlations (r2 > 0.99, p < 0.0001) for each formulation. Qualitative rank order correlations were observed among all combinations of in-vivo and in-vitro parameters. These data support a Level A correlation between in-vivo absorption profiles and in-vitro release rates of four pseudoephedrine sulfate extended release formulations determined in fasted healthy volunteers.
Mojaverian
P
P
Department of Drug Metabolism & Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Rosen
J
J
Vadino
W A
WA
Liebowitz
S
S
Radwanski
E
E
D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004809:Ephedrine / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D011897:Random Allocation; D012044:Regression Analysis; D014662:Vasoconstrictor Agents / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D014662:Vasoconstrictor Agents; D004809:Ephedrine