Organic acids as excipients in matrix granules for colon-specific drug delivery.
Interest exists in developing site-specific systems for release of a drug in the lower part of the small intestine or in the colon. The aim of this study was to investigate whether drug release rates from enteric matrix granules could be influenced by using organic acids as excipients. Ibuprofen was used as a model drug and Eudragit S and Aqoat AS-HF as enteric polymers. The dissolution rates of the drug were investigated at different levels of pH (5.8, 6.8 and 7. 4). Drug absorption was studied in bioavailability tests in healthy volunteers. In vitro/in vivo correlation was also investigated. It was concluded that although inclusion of an organic acid in a formulation retarded in vitro release of the model drug, no corresponding effect was evident in in vivo studies. Bioavailability tests are therefore important early on during development of new dosage forms or formulations. Although no correlation between in vitro and in vivo results was generally evident correlation could be demonstrated for individual formulations following mathematical transformation of data.
Nykänen
P
P
Division of Biopharmaceutius and Pharmacokinetics, Department of Pharmacy, University of Helsinki, P.O.Box 56, FIN-00014, Helsinki, Finland.
Krogars
K
K
Säkkinen
M
M
Heinämäki
J
J
Jürjensson
H
H
Veski
P
P
Marvola
M
M
D000143:Acids / Q000737:chemistry; D000328:Adult; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D003106:Colon / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011208:Powders; D012995:Solubility; D013608:Tablets, Enteric-Coated
D000143:Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011208:Powders; D013608:Tablets, Enteric-Coated; D007052:Ibuprofen