Cinacalcet hydrochloride-nanoemulsion: preparation, characterization, enhanced bioavailability and pharmacodynamics

J. Wang, G.-G. Chen, L.-L. Ren

School of Pharmacy, Nanjing Tech University, Nanjing, China. renlili@njtech.edu.cn

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• Pharmacology

OBJECTIVE: The aim of the study was to improve the bioavailability of Cinacalcet hydrochloride (CLC) and enhance its efficacy by the nanoemulsion drug delivery system.

MATERIALS AND METHODS: First, cinacalcet hydrochloride-nanoemulsion (CLC-NE) was prepared and optimized through the pseudo ternary phase diagram and central composite design response surface methodology (CCD). The release of CLC-NE in vitro was investigated with four different dissolution media, and the bioavailability of CLC-NE in vivo was studied through beagle dogs. Finally, the pharmacodynamics of CLC-NE was evaluated by the rat model of uremia.

RESULTS: Oleic acid, op-10, and PEG-200 were selected as oil phase, emulsifier, and co-emulsifier, respectively. The optimum ratio of oleic acid, op-10, PEG-200, and water was 9.87%, 38.33%, 12.78%, and 39.02%. CLC-NE has similar dissolution rates in different pH media, and the relative bioavailability of CLC-NE was 166.5%. The uremia model showed that CLC-NE could enhance renal function and reduce the excessive phosphorus (P), serum creatinine (Scr), and urea nitrogen (Urea) of model rats, as well as the inhibited increase of fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH).

CONCLUSIONS: The solubility, bioavailability, and pharmacodynamics of CLC can be significantly improved through the nanoemulsion drug delivery system.

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