Objective: The purpose of this study was to investigate the dissolution and oral bioavailability of an immediate-release tablet involving wet grinding of a poorly water-soluble drug, fenofibrate.
Methods: The milled suspension was prepared using a Basket Dispersing Mill in the presence of a hydrophilic polymer solution and then granulated with common excipients, and compressed into an immediate-release tablet with blank microcrystalline cellulose granules.
Results: Compared with unmilled tablets (56% within 30 minutes), the dissolution of wet-milled tablets (about 98% in 30 minutes) was markedly enhanced. No significant decrease in the dissolution rate (96% in 30 minutes) of the wet-milled tablet was observed after 3 months under 40 degrees C and 75% relative humidity storage. In addition, the oral bioavailability of the wet-milled tablets (test) and Lipanthyl supra-bioavailability tablets (reference) was determined in beagle dogs after a single dose (160 mg fenofibrate) in a randomized crossover, own-control study. The results suggested that both the area under the plasma concentration-time curve (AUC((0-t)) = 46.83 +/- 11.09 microg/mL h) and the mean peak concentration of the test (C(max) = 4.63 +/- 1.71 microg/mL) were higher than the reference (AUC((0-t)) = 35.12 +/- 10.97 microg/mL h, C(max) = 2.11 +/- 0.08 microg/mL). The relative bioavailability of the wet-milled tablet was approximately 1.3-fold higher. Furthermore, the apparent rate of absorption of fenofibrate from the wet-milled tablet (T(max) = 2.63 hours) was faster than that from Lipanthyl (T(max) = 3.75 hours).
Conclusion: These results indicated that the dissolution and the bioavailability of fenofibrate were significantly enhanced by wet-grinding process. So, this shows that wet grinding is a powerful technique to improve the bioavailability for poorly water-soluble drugs, especially for Biopharmaceutics Classification System Class II compounds.