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

Abstract

Objective: The objective of the present research is to formulate solid lipid nanoparticles (SLN) of CH to improve its oral bioavailability.Methods: 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.Results: 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 vis-a-vis 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.Conclusion: Thus lyophilized SLN formulation explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery and stability of CH.

Keywords: Cinacalcet HCl; bioavailability; hot homogenization; stability study; ultrasonication.