Lyophilized SLN of Cinnacalcet HCl: BBD enabled optimization, characterization and pharmacokinetic study.

The objective of the present research is to formulate solid lipid nanoparticles (SLN) of CH to improve its oral bioavailability. Cinnacalcet hydrochloride (CH) exhibits poor oral bioavailability of 20 to 25% because of low aqueous solubility and first pass metabolism. The SLN formulations were optimized using Box-Behnken Design. SLN formulation was prepared using hot homogenization technique followed by ultra-sonication and evaluated. The optimized SLN formulation was lyophilized to improve the stability of the formulation further. Compritol 888 ATO (COM), Soya lecithin (SL) and poloxamer 188 (POL) were selected as lipid, surfactant and co-surfactant respectively. For optimistaion, the desirable goal was fixed for variour responses entrapment efficiency (EE), particle size (PS) and (time taken for diffusion of 85% drug) T85%. The optimized single dose of SLN obtained using BBD consisting of 30 mg of CH, 100 mg of COM, 150 mg of SL and 0.1% w/v of POL. The pharmacokinetic study revealed that optimized SLN and lyophilized SLN were found to increase the oral bioavailability nearly two times compared to an aqueous suspension of pure drug. Thus lyophilized SLN formulation explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery and stability of CH.