Solid Dispersion of Kaempferol: Formulation Development, Characterization, and Oral Bioavailability Assessment

Abstract

Kaempferol (KPF), an important flavonoid, has been reported to exert antioxidant, anti-inflammatory, and anticancer activity. However, this compound has low water solubility and hence poor oral bioavailability. This work aims to prepare a solid dispersion (SD) of KPF using Poloxamer 407 in order to improve the water solubility, dissolution rate, and pharmacokinetic properties KPF. After optimization, SDs were prepared at a 1:5 weight ratio of KPF:carrier using the solvent method (SDSM) and melting method (SDMM). Formulations were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) analysis, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The solubility in water of carried-KPF was about 4000-fold greater than that of free KPF. Compared with free KPF or the physical mixture, solid dispersions significantly increased the extent of drug release (approximately 100% within 120 min) and the dissolution rate. Furthermore, after oral administration of SDMM in rats, the area under the curve (AUC) and the peak plasma concentration (Cmax) of KPF from SDMM were twofold greater than those of free KPF (p < 0.05). In conclusion, SD with Poloxamer 407 is a feasible pharmacotechnical strategy to ameliorate the dissolution and bioavailability of KPF.

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Funding

This study was financially supported by CAPES-MEC, Brazil (Network Nanobiotec—grant no. 902/2009 and PROCAD—grant no. 552457/2011-6), CNPq (grant no. 453927/2014-9), and FAPERGS (Edital PqG 2017-T.O. 17/2551-0001043-4 and 17/2551-0000 970-3). M.C. thanks CAPES for her scholarship.

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Correspondence to Letícia Scherer Koester.

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Colombo, M., de Lima Melchiades, G., Michels, L.R. et al. Solid Dispersion of Kaempferol: Formulation Development, Characterization, and Oral Bioavailability Assessment. AAPS PharmSciTech 20, 106 (2019). https://doi.org/10.1208/s12249-019-1318-y

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KEY WORDS

  • kaempferol
  • Poloxamer 407
  • solid dispersion
  • dissolution
  • bioavailability