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

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.

Highlights

Gastro-retentive drug delivery system of neratinib (NTB) was established.

The formulation was developed via effervescent technique for breast cancer treatment.

The release of NTB from optimized formulation showed sustained release profile for up to 12 h.

Cytotoxicity studies indicated that NTB in an optimized formulation was more efficacious than free NTB.

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.

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Article information: Mohamed Rahamathulla, Saad M. Alsahhrani, Ahmed Al Saqr, Abdullah Alshetaili, Faiyaz Shakeel, Effervescent floating matrix tablets of a novel anti-cancer drug neratinib for breast cancer treatment, Journal of Drug Delivery Science and Technology, 2021. https://doi.org/10.1016/j.jddst.2021.102788.