IN-VITRO AND IN-VIVO EVALUATION OF A XANTHAN GUM-N-OCTENYLSUCCINATE STARCH MATRIX TABLET CONTAINING IBUPROFEN AS A MODEL-DRUG

The bioavailability after oral administration of two sustained release ibuprofen formulations using xanthan gum and a combination of n-octen ylsuccinate starch (CL490) and xanthan gum has been investigated in he althy human volunteers and compared with a commercial suspension formu lation. The ibuprofen-xanthan gum and the ibuprofen-xanthan gum-CL490 matrix tablets were prepared by:direct compression. Three different xa nthan gum/CL490 ratios (1:1; 1:4 and 1:10) were investigated in vitro. The xanthan gum/CL490 matrix tablets of a 1/4 and a 1/10 ratio both r eleased nearly 100% after 24 h. No difference was observed in the rele ase profiles between the matrix tablets prepared with 1/1 ratio of xan than gum and CL490 and with pure xanthan gum during the first 8 h of d issolution test. After 8 h, the release rate from the pure xanthan gum matrix increased (nearly 90% after 24 h) while matrix tablet with a 1 /1 ratio of xanthan gum and CL490 released 60% after 24 h. A dry core remained after a 24 h dissolution time period for matrix tablets prepa red with the 1/1 ratio of xanthan gum and CL490, while the pure xantha n gum matrix had completely eroded. For the in vivo study, a xanthan g um/CL490 (1:1) matrix tablet was compared to a xanthan gum matrix tabl et and a conventional suspension formulation. In comparison with the c onventional suspension, the oral bioavailability was 86.83% +/- 25.80% (n = 6) and 75.50% +/- 17.18% (n = 6) for the tablets made with xanth an gum and with a combination of xanthan gum and CL490 (ratio 1/1), re spectively. The combination of a xanthan gum and CL490 seemed to avoid the initial slow absorption phase in vivo that occurred with a pure x anthan gum matrix tablet. The combination of xanthan gum and n-octenyl succinate starch could offer some advantages in the formulation of sus tained release hydrophilic matrix tablets.