Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine

Int J Pharm. 2019 Apr 20;561:9-18. doi: 10.1016/j.ijpharm.2019.02.027. Epub 2019 Feb 25.

Abstract

Curcumin (CUR) has gained increasing interest worldwide due to multiple biological activities. However, the therapeutic application remains limited because of its low aqueous solubility, intestinal metabolism and poor membrane permeability. In present study, an excipient-free CUR solid dispersion co-formed with piperine (PIP), the absorption enhancer involving metabolism-permeability, was successfully prepared by melting and quench cooling (co-amorphous CUR-PIP). The co-amorphous CUR-PIP exhibited superior performance in non-sink dissolution compared with crystalline and amorphous CUR, and showed physically stable at least 3 months, attributing to the strong molecular interactions between CUR and PIP as evaluated by FTIR spectra. Furthermore, the combination of PIP with CUR in the co-amorphous formulation could inhibit the glucuronidation of CUR, as exhibited in the in vitro assay of rat intestinal microsomes. The co-amorphous CUR-PIP would also exhibit higher gastrointestinal membrane permeability of CUR, as confirmed by Papp of CUR in Caco-2 model. After administration of co-amorphous CUR-PIP, the AUC of CUR significantly increased by 2.16- and 1.92-fold those in crystalline and amorphous CUR, respectively. This study demonstrates that the developed co-amorphous CUR-PIP can enhance the bioavailability of CUR by increasing its dissolution, inhibiting metabolic processes, and facilitating membrane permeability.

Keywords: Bioavailability; Co-amorphous; Curcumin; Membrane permeability; Metabolic inhibition; Piperine.

MeSH terms

  • Alkaloids / chemistry
  • Animals
  • Benzodioxoles / chemistry
  • Biological Availability
  • Cells, Cultured
  • Curcumin / chemistry
  • Curcumin / pharmacokinetics*
  • Drug Delivery Systems / methods*
  • Drug Stability
  • Humans
  • Intestinal Absorption*
  • Intestinal Mucosa / metabolism
  • Piperidines / chemistry
  • Polyunsaturated Alkamides / chemistry
  • Rats
  • Solubility

Substances

  • Alkaloids
  • Benzodioxoles
  • Piperidines
  • Polyunsaturated Alkamides
  • Curcumin
  • piperine