Bicalutamide nanocrystals with improved oral bioavailability: in vitro and in vivo evaluation

Abstract

Context: Bicalutamide (BCT) is an antiandrogenic compound belonging to Biopharmaceutics Classification System (BCS) class II drug. Thus it has limited aqueous solubility and hence limited oral bioavailability.

Objective: The purpose of the present investigation was to obtain stable nanocrystals of BCT with improved kinetic solubility, dissolution and pharmacokinetic profiling.

Materials and methods: BCT nanocrystals were prepared by antisolvent precipitation method using Soluplus, a novel amphiphilic polymer. Nanocrystals were characterized for particle size, powder X-ray diffraction analysis (PXRD), in vitro dissolution, in vivo pharmacokinetic profile and stability.

Results and discussion: The obtained nanocrystals had particle size of 168 nm and were spherical in shape. The nanocrystals exhibited fivefold increase in kinetic solubility as compared to pure drug and 85% dissolution in 60 min. PXRD studies established the retention of crystalline polymorphic form II. The in vivo pharmacokinetic study demonstrated that the C_max and AUC of nanosized BCT were about 3.5 times higher as compared to pure drug.

Conclusion: Nanosizing of BCT significantly improved the pharmacokinetic profile of the drug administered to rats. Prepared nanocrystals were found to be stable over the entire stability period. Thus the use of amphiphilic polymer like Soluplus singularly helped in efficient size reduction and stabilization of the drug.

Keywords::

• Bicalutamide
• nanocrystals
• antisolvent precipitation
• amphiphilic stabilizer
• dissolution properties
• pharmacokinetic studies

Acknowledgement

The authors thank Wockhardt Limited (Aurangabad, India) and Sun Pharma (Mumbai, India) for providing gift sample of BCT and Letrozole, respectively. The authors thank BASF Corporation for providing gift samples of excipients.

Declaration of interest

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