The Effect of Excipient Solubility on the in-vitro and in-vivo Properties of Bendrofluazide Tablets 5 MG

SUMMARY

TaRblets containing bendrofluazide 5 mg have been prepared at 190, 220 and 290 MNm^-2 using four different excipients; sorbitol, lactose, calcium orthophosphate and calcium hydrogen orthophosphate. The solubilities in water of the excipients were respectively 70, 17.8, 0.03 and 0.01% W/W. Granules prepared under identical conditions were found to have moisture contents of about 3% W/W. All the four excipients were found to be equally effective in producing minimal tablet to tablet weight variation. Tablet hardness was governed by the intrinsic nature of the excipient and for all diluents an increase in compressional force produced an increase in tablet hardness. However, the size of this hardness increase varied markedly dependent on the excipient. Disintegration time and the nature of the disintegrating process varied greatly with the excipient. Generally, decreasing the solubility of the diluent decreased the disintegration time, but the pattern was complicated by the effect of compaction pressure which produced marked disintegration time differences with some excipients but not with others. No correlation was found between disintegration time and dissolution rate. However changing the excipient greatly affected the dissolution rates of the tablets in some cases by as much as 600%. Disintegration time was found to be no indicator of dissolution performance. In-vivo assessment of the tablets demonstrated that there was a direct correlation between in-vivo activity, measured as initial micturation rate, with bendro-fluazide dissolution. In general the study showed that by changing the diluent, marked differences in the in-vivo and in-vitro properties of the bendrofluazide tablets could be demonstrated and that these differences were more marked using very soluble excipients. The best excipients were found to be calcium orthophosphate and calcium hydrogen orthophosphate. Sorbitol was found to be the least useful as a tablet diluent.