Effervescent floating matrix tablets of a novel anti-cancer drug neratinib for breast cancer treatment

Abstract

The main purpose of this study was to develop a novel gastro-retentive drug delivery system via effervescent technique for the treatment of breast cancer. Neratinib (NTB) is a novel anticancer drug, poorly soluble at higher pH, was been used as a model drug and an attempt was made to develop a floating tablet using hydroxypropyl methylcellulose-90SH 15000 (HPMC-90SH 15000), microcrystalline cellulose, sodium bicarbonate, talc and lactose using direct compression method. The particulate materials were studied for the pre-compression parameters before compression. After compression, the floating matrix tablets of NTB were developed and studied in terms of post-compression parameters, floating lag time, buoyancy evaluation, water uptake/swelling studies, in vitro release, release kinetics and cytotoxicity studies. The parameters of pre- and post-compression evaluation were within the limits of United States Pharmacopoeia. Fourier transform infra-red evaluation indicated no interaction between the NTB and excipients used. The developed floating matrix tablets of NTB showed good swelling/floating properties for more than 24 h, and floating lag time was within 120 s. The NTB release from an optimized formulation G2 (100% release) offered a sustained release profile for up to 12 h. The release mechanism of NTB from formulation G2 was non-Fickian release mechanism. Cytotoxicity evaluation on MCF-7 human breast cancer cells suggested that NTB in an optimized formulation G2 (cytotoxicity = 98.60% at 800 nM) was more efficacious than free NTB (cytotoxicity = 91.29% at 800 nM). All these results and observations suggested that developed floating matrix tablets of NTB could be effectively applied for the treatment of breast cancer.