Effects of pH regulators used as additives on the bioavailability of ibuprofen from hard gelatin capsules.
In our previous study the reasons for fast absorption of ibuprofen from sodium bicarbonate based hard gelatin capsules stayed unclear. These were not investigated using pH regulators (aluminium hydroxide, calcium carbonate, tartaric acid) with different chemical and physical properties. Ibuprofen absorption was much slower with aluminium hydroxide capsules (MRT 5.3, Tmax 3.1 h, Cmax 25.6 mg l-1, lag time 37.5 min) than with sodium bicarbonate capsules of the previous study (MRT 2.6 h, tmax 0.4 h, Cmax 51.4 mg l-1), lag time 0 min). The corresponding values for calcium carbonate and tartaric acid capsules were: MRT 3.7 h and 3.9 h, Tmax 1.7 h and 2.0 h, Cmax 32.2 mg l-1 and 30.8 mg l-1 and lag time 3.1 min and 7.6 min. No differences were noted in the AUC values. A rank order correlation existed between dissolution parameters and the in vivo parameters reflecting the rate of bioavailability. It was concluded that the rapid absorption of ibuprofen from capsules containing sodium carbonate is due to enhanced in vivo disintegration of the capsule, enhanced in vivo dissolution of the drug and enhanced gastric emptying rate.
Hannula
A M
AM
University Pharmacy, University of Helsinki, Finland.
Marvola
M
M
Rajamaeki
M
M
Ojantakanen
S
S
D000328:Adult; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D001682:Biological Availability; D002119:Calcium Carbonate / Q000494:pharmacology*; D002214:Capsules; D005079:Excipients; D005260:Female; D005780:Gelatin; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D012995:Solubility; D013644:Tartrates / Q000494:pharmacology*
D002214:Capsules; D005079:Excipients; D013644:Tartrates; D000536:Aluminum Hydroxide; D005780:Gelatin; D002119:Calcium Carbonate; D007052:Ibuprofen