Evaluation of pantoprazole formulations in different dissolution apparatus using biorelevant medium.
OBJECTIVE
The study was developed to compare the in vitro dissolution profiles of pantoprazole (CAS 102625-70-7) formulations in both The United States Pharmacopeia (USP) apparatus 2 and 3 by applying biorelevant medium. Moreover, an in vitro-in vivo relationship was proposed considering in vivo data from a previously published study.


METHODS
In vitro dissolution profiles were evaluated in biorelevant medium in USP apparatus 2 and 3 and the dissolution curves were either compared by the similarity factor (f2) or a model-independent approach. The fraction of drug dissolved in vitro in apparatus 2 was compared with the fraction of drug absorbed in vivo, which was obtained from a retrospective in vivo study. An in vitro-in vivo relationship analysis was then applied to elucidate the overall absorption characteristics of formulations.


RESULTS
The dissolution profiles of formulations demonstrated similar disposition in biorelevant medium in both USP apparatus 2 and 3. The dissolution profiles were described by f2 model in apparatus 2 and Weibull's function in apparatus 3. The vitro-in vivo relationship analysis showed that the formulations exhibited permeability rate-limiting absorption.


CONCLUSIONS
Biorelevant medium in both USP apparatus 2 and 3 may be used as a tool to predict in vivo disposition of formulations of pantoprazole. Furthermore, it can be argued that biowaiver can be granted for enteric coated formulations of pantoprazole on the basis of in vitro dissolution profile.
de Campos
Daniel Rossi
DR
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Braganga Paulista, SP, Brazil. cinetica04@yahoo.com.br
Klein
Sandra
S
Zoller
Thomas
T
Vieria
Nelson Rogério
NR
Barros
Fábio Alessandro Proença
FA
Meurer
Eduardo César
EC
Coelho
Edvaldo Capobiango
EC
Marchioretto
Marco Antônio
MA
Pedrazzoli
José
J
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000737:chemistry*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005079:Excipients; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D012189:Retrospective Studies; D012995:Solubility; D013608:Tablets, Enteric-Coated
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D005079:Excipients; D054328:Proton Pump Inhibitors; D013608:Tablets, Enteric-Coated; D000077402:Pantoprazole