23 Factorial Design and Optimization of Effervescent Floating Matrix Tablet of Neratinib

Purpose

The main objective of the research was to formulate an effervescent floating matrix tablet (EFMT) of a potential anticancer drug neratinib employed in breast cancer therapy. The drug shows poor aqueous solubility at higher pH leading to reduce therapeutic efficacy, thereby resulting in poor bioavailability. Hence, an EFMT is designed to extend the gastric residence time (GRT) of drugs, which can remain several hours in the gastric region and enhance bioavailability. Further 2³ factorial design employed.

Methods

The EFMT of neratinib are prepared by direct compression using hydroxyl propyl methylcellulose, Carbopol 940, microcrystalline cellulose, sodium bicarbonate, talc, and lactose. Polymer concentrations were selected as independent variables, whereas hardness, percentage swelling, floating, and percentage drug release were the dependent variables. Pre- and post-compression measurements, swelling studies, in vitro buoyancy, FTIR, scanning electron microscopy (SEM), in vitro release, kinetic, and mechanism of drug release studies have been characterized for preparing floating matrix tablets

Results

The results showed that pre-and post-compression parameters are within the limit of USP. The buoyancy lag time and total buoyancy time are less than 2 min and > 12 h, respectively, with good swelling characteristics. Fourier transform infrared (FTIR) spectrum showed that no interaction was found between drug and polymers. The optimized formulation (F9) showed 100% drug release at 8 h, which shows a Fickian diffusion.

Conclusion

The developed novel neratinib floating matrix tablet could enhance the solubility and residence time of neratinib at upper GIT because of the combined effect of the polymers.