Preparation of fenofibrate immediate-release tablets involving wet grinding for improved bioavailability

Abstract

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°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 μg/mL h) and the mean peak concentration of the test (C_max = 4.63 ± 1.71 μg/mL) were higher than the reference (AUC_(0−t) = 35.12 ± 10.97 μg/mL h, C_max = 2.11 ± 0.08 μg/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.

Keywords:

• Dissolution
• fenofibrate
• hydrophilic polymer
• oral bioavailability
• particle size reduction
• wet grinding

Acknowledgments

Dr. David B. Jack is gratefully thanked for correcting the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.