Citric acid as a pH-regulating additive in granules and the tablet matrix in enteric-coated formulations for colon-specific drug delivery.
Colon-specific drug-delivery systems have been extensively investigated over the last decade. The aim of the study reported here was to investigate whether times of commencement of drug liberation and absorption could be controlled by varying the amount of citric acid in granule cores or in the tablet matrix in enteric-coated multiple-unit tablets. One of the most important aims was to determine the optimal amounts and locations of citric acid in formulations intended as drugs targeted at the colon. Ibuprofen was used as the model drug. Drug release rates were studied in phosphate buffer at pH 6.8 and 7.4. A gradient dissolution study at pH 1.2, 6.8 and 7.4 was undertaken with two formulations. Drug absorption was studied by means of bioavailability tests. We concluded that the drug release rate could be controlled in vitro by changing the amount of citric acid in granule cores or the tablet matrix. In vivo tests confirmed that between 10 and 15% citric acid in the tablet matrix delayed the commencement of drug absorption most. This kind of formulations could be suitable for preparation of colon-specific dosage forms. It is probably unnecessary to include citric acid in granule cores. No logical correlation between in vitro and in vivo results was obtained.
Nykänen
P
P
Division of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, University of Helsinki, Finland. pirjo.nykanen@helsinki.fi
Sten
T
T
Jürjenson
H
H
Veski
P
P
Marvola
M
M
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D019343:Citric Acid / Q000737:chemistry*; D003106:Colon / Q000502:physiology*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry; D007408:Intestinal Absorption; D008297:Male; D011208:Powders; D012995:Solubility; D013608:Tablets, Enteric-Coated
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011208:Powders; D013608:Tablets, Enteric-Coated; D019343:Citric Acid; D007052:Ibuprofen