International journal of pharmaceutics vol:169 issue:1 pages:105-113
The controlled-release (CR) properties of xanthan gum (XG) matrix tablets were investigated in vivo. Indomethacin and the sodium salt of indomethacin were selected as model drugs to examine the properties of formulations of a very poorly soluble and a highly soluble drug, respectively. The performance of XG matrices was compared with a marketed CR product containing an equivalent dose of indomethacin. A single oral dose pharmacokinetic study was conducted according to a randomised crossover design in six healthy male volunteers with three dosage forms: (A), 50 mg indomethacin tablets; and (B), 50 mg sodium indomethacin tablets both prepared with XG; and (C) Flexin(R) tablets. Dosage forms A and C showed the same in vitro release profile, while dosage form B demonstrated a faster release of the drug. There was no statistically significant difference in the time to reach the maximal plasma concentration between dosage form A and B or the reference product. Whereas the maximal plasma concentrations were varied considerably and found to be 1.73, 1.07, and 0.73 mu g/ml for the dosage form A, B, and C, respectively. No statistically significant difference in AUC(0-32) was found between either of the two test products and the reference product, but three way analysis of variance indicated an influence of the variable 'volunteers' on this parameter, indicating that interpretation of these data must be done with great caution. Based on these findings, the three products can be considered as bioequivalent. However, it seems that the drug released from the test products reached the minimum effective concentration earlier and remained longer within the therapeutic range. Based on these findings, it can be concluded that, although the common pharmacokinetic parameters of the drug from the test products are not significantly different from those of the marketed product, the therapeutic efficacy of the drug from the former may be superior to that of the latter. (C) 1998 Elsevier Science B.V. All rights reserved.