IN-VIVO EVALUATION OF XANTHAN GUM AS A POTENTIAL EXCIPIENT FOR ORAL CONTROLLED-RELEASE MATRIX TABLET FORMULATION

The controlled-release (CR) properties of xanthan gum (XG) matrix tabl ets were investigated in vivo. Indomethacin and the sodium salt of ind omethacin were selected as model drugs to examine the properties of fo rmulations of a very poorly soluble and a highly soluble drug, respect ively. The performance of XG matrices was compared with a marketed CR product containing an equivalent dose of indomethacin. A single oral d ose pharmacokinetic study was conducted according to a randomised cros sover design in six healthy male volunteers with three dosage forms: ( A), 50 mg indomethacin tablets; and (B), 50 mg sodium indomethacin tab lets 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 de monstrated a faster release of the drug. There was no statistically si gnificant difference in the time to reach the maximal plasma concentra tion between dosage form A and B or the reference product. Whereas the maximal plasma concentrations were varied considerably and found to b e 1.73, 1.07, and 0.73 mu g/ml for the dosage form A, B, and C, respec tively. No statistically significant difference in AUC(0-32) was found between either of the two test products and the reference product, bu t three way analysis of variance indicated an influence of the variabl e 'volunteers' on this parameter, indicating that interpretation of th ese 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 effe ctive concentration earlier and remained longer within the therapeutic range. Based on these findings, it can be concluded that, although th e common pharmacokinetic parameters of the drug from the test products are not significantly different from those of the marketed product, t he therapeutic efficacy of the drug from the former may be superior to that of the latter. (C) 1998 Elsevier Science B.V. All rights reserve d.