In vitro and in vivo evaluation of carbamazepine-PEG 6000 solid dispersions

The present work extended previous physico-chemical investigations on the e ffects of solid dispersion on the solubility, the dissolution rate and the pharmacokinetic profile of carbamazepine. Solubility studies showed a linea r increase in carbamazepine solubility with the increase of PEG 6000 concen tration. There is no marked difference between physical mixtures and solid dispersions for the enhancement of carbamazepine solubility, by PEG 6000. L ess than 60% of pure carbamazepine was dissolved in 90 min. Physical mixtur es (carbamazepine phase III) and solid dispersions (carbamazepine phase II) dissolution rates were higher in comparison of the parent drug. The dissol ution of carbamazepine phase III was more pronounced than that evoked by th e phase II. The dissolution profiles indicated that the percentage of the d rug dissolved was dependent on the proportion of PEG 6000. In solid dispers ions there was a remarkable enhancement in the dissolution rates of the dru g in the vicinity of the eutectic composition as compared with those of cor responding physical mixtures. Hence, the optimum value for the solid disper sion was 80.5 +/- 1.7% of carbamazepine having dissolved within the first 1 0 min compared to 40 +/- 1% for the corresponding physical mixtures of the same composition. Statistical analysis of pharmacokinetic parameters confir med that the carbamazepine:PEG 6000 binary systems displayed higher bioavai lability of the drug than the pure carbamazepine. The area under the curve (AUC) values highlighted the evidence that only slight differences in the b ioavailability of the drug occur between physical mixtures and solid disper sions prepared at the 80:20 and 50:50 drug:carrier compositions. However, t he mean normalized plasma concentrations showed that standard error deviati ons are rather wide intervals for pure drug and physical mixtures in compar ison to solid dispersions. One additional interesting point to consider is the disappearance of the multiple peaks on the individual kinetic curves of the 50:50 solid dispersion composition. Furthermore, our investigations ha ve highlighted the interest of solid dispersions prepared at much less than near much greater than -eutectic composition as our preliminary data show that the plasma concentration (C-5h of the drug for the 15:85 dispersed sam ple containing 150 mg of carbamazepine is not significantly different from that obtained for the 50:50 dispersed sample containing 300 mg of the drug. (C) 2001 Elsevier Science BN. All rights reserved.