Solid dispersion of fenofibrate （FNB）, a poorly water-soluble drug, was prepared by a fluid-bed coating technique with PEG 6000 as the carrier. The physical state was characterized by DSC and X-ray powder diffractometry, which indicated the existence of fenofibrate in crystalline form in the solid dispersion. In vitro dissolution was studied in water containing 1% sodium lauryl sulfate, FASSIF and FESSIF. Significant enhancement in dissolution was achieved at PEG/FNB ratio of 4/1 with near complete dissolution within 30 min. Moderate improvement in dissolution rate was observed at smaller PEG/FNB ratios. Oral bioavailability was studied in beagle dogs after oral administration of fenofibrate solid dispersion pellets by monitoring fenofibric acid in plasma. The oral bioavailability of PEG/FNB 3/1 and 4/1 solid dispersion pellets was improved by 3.4 and 4.4-fold as compared to Lipanthyl, a commercial micronized fenotibrate formulation. There was a strong dependence of oral bioavailability on the in vitro dissolution rate. Good correlation was observed between the in vivo absorption fraction and the in vitro dissolution rate in each of the dissolution media, water containing 1% sodium lauryl sulfate, FASSIF and FESSIF. It could be concluded that PEG/FNB solid dispersion pellets were able to improve the dissolution and oral bioavailability of fenofibrate.
We studied the effect of two independent variables, the pectin/calcium chloride weight ratio and the overall matrix weight in HPMC/pectin/calcium matrix tablet, on the release of indomethacin. A two-factor 5-level central composite experimental design was employed. Responses of the Peppas correlation parameters n and K and the 10% release time （T0.1） were optimized by response surface methodology. Significant effect of the independent variables on the biphasic release parameters, n and K, was observed. N, K and T0.1 were well fitted with the second-order quadratic equations rather than linear equations. Moreover, the mathematic fitting and the response surfaces showed significant cross-interaction between the pectin/calcium chloride ratio and the overall matrix weight. The optimal formulation with larger n, longer T0.1 and smaller K consisted of medium pectin/calcium chloride ratio around 1.0 and medium matrix weight around 200 mg. Validation studies on the optimal formulations showed good predictability of the n, K and T0.1 values with biases within the range of-7.33% and 6.26%. Our results support that central composite design can be used to optimize drug release from HPMC/pectin/calcium matrix tablet with high predictability.
