Nanostructured Lipid Carrier of Cinacalcet HCl: Formulation, BBD Enabled Optimization, Pharmacokinetic and In-Vitro Cytotoxicity Study

Background: Cinacalcet hydrochloride (CINH) is a BCS class IV drug. It is mainly used for the treatment of chronic renal disease and parathyroid cancer. It exhibits poor oral bioavailability of less than 25%. Objectives: The main objective is to improve the bioavailability of CINH by formulating the nanostructure lipid carrier (NLC). Methods: In this research, glyceryl monostearate (GMS), labrasol, and tween 20 were the main excipients selected for the formulation of NLC. Hot high-speed homogenization and ultra-sonication method was used for the NLC formulation of CINH. The characterization of the NLCs was done as per standard procedures. Optimization of the formulated NLC was carried out by applying Box- Behnken Design (BBD) with the help of the Design Expert software. The pharmacokinetic study was conducted to determine the improvement in the bioavailability of the CINH. The cytotoxicity study was performed by using the MTT assay method to know the cell viability. Results: The optimized NLC formulation exhibited high drug content with a particle size of less than 200nm. A pharmacokinetic study showed 4 fold increase in oral bioavailability for the optimized NLC in comparison to the aqueous suspension of CINH. Minimum viability was determined as 94%, which indicates the safety of the incubated formulations. Conclusion: NLC formulation has the potential to improve oral bioavailability with high drug loading and cell viability for CINH.