Citric acid as excipient in multiple-unit enteric-coated tablets for targeting drugs on the colon.
Delivery of drugs to the large bowel has been extensively investigated during the last decade. The aim of this study was to investigate whether enteric-coated tablets could be made from enteric-coated matrix granules and drug release targeted to the colon. Whether in vitro drug release rate and in vivo absorption could be delayed by adding citric acid to the granules and/or to the tablet matrix was also studied. Ibuprofen was used as model drug because it is absorbed throughout the gastrointestinal tract. Eudragit S and Aqoat AS-HF were used as enteric polymers. Drug release rates were studied at different pH levels and drug absorption was studied in bioavailability tests. The conclusion was that citric acid retarded in vitro drug release when used in multiple-unit tablets. In vivo absorption of ibuprofen was markedly delayed when citric acid was included in both granules and tablet matrix. Further studies are needed to determine the optimal amount of citric acid in formulations.
Nykänen
P
P
Division of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, University of Helsinki, PO Box 56, FIN-00014, Helsinki, Finland.
Lempää
S
S
Aaltonen
M L
ML
Jürjenson
H
H
Veski
P
P
Marvola
M
M
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D019343:Citric Acid / Q000737:chemistry*; D003106:Colon / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D011208:Powders; D012995:Solubility; D013608:Tablets, Enteric-Coated
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011208:Powders; D013608:Tablets, Enteric-Coated; D019343:Citric Acid; D007052:Ibuprofen