Preparation of loratadine nanocrystal tablets to improve the solubility and dissolution for enhanced oral bioavailability.

Objectives: Loratadine is a selective H1 receptor inhibitor that has been widely used in the clinical treatment of allergic diseases. Here we aimed to develop a novel solid loratadine nanocrystal to increase the low and pH-dependent water solubility for bioavailability enhancement.

Methods: Loratadine solid nanocrystal was developed through high-speed shear-high pressure homogenization followed by freeze-drying, which was further prepared into tablets through direct compression. The formulation and process parameter were screened. Furthermore, the characterization and oral bioavailability of loratadine nanocrystal were studied.

Key Findings: The loratadine nanocrystal had the satisfactory particle size of 425.9 nm and great redispersibility, which was mainly attributed to the addition of Pluronic F127 and polyvinylpyrrolidone K17 as the stabilizer. The saturation solubility of the loratadine nanocrystal was increased to 3.81, 3.22 and 2.57-fold that of the crude drug in water, pH 6.8 and pH 4.5 buffer respectively. Furthermore, the pharmacokinetic studies in rats revealed that the AUC (0-∞) of the nanocrystal tablets was 2.38-fold that of raw tablets and 1.94-fold that of commercial tablets, respectively.

Conclusions: The nanocrystal tablets could significantly improve the oral bioavailability of loratadine, which would also be a promising approach to enhance the solubility of insoluble drugs.