Preparation, characterization, and pharmacokinetics study of capsaicin via hydroxypropyl-beta-cyclodextrin...

Capsaicin (CAP) is an effective drug in the treatment of pain and cancer. However, its practical administration has been limited due to poor aqueous solubility and bioavailability, as well as strong gastrointestinal irritation.

The objective of this study is to improve the solubility and oral bioavailability of CAP by reducing irritation via hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex formulation, in vitro and in vivo analysis.

The complex (CAP-HP-β-CD) was developed via the magnetic stirring method and characterized using ultraviolet (UV) absorption spectrometry, infrared radiation (IR) spectroscopy, and differential scanning calorimetry (DSC). Rats were treated with CAP (90 mg × kg(-1)) or CAP-HP-β-CD (corresponding to 90 mg × kg(-1) CAP) by gavage, and all the plasma samples were analyzed with high performance liquid chromatography (HPLC).

The results of UV, IR, and DSC showed that an acceptable CAP-HP-β-CD (encapsulation efficiency, 75.83%; drug loading, 7.44%) was formulated. In vitro release study of CAP-HP-β-CD revealed that the cumulative release of CAP from HP-β-CD encapsulation was obviously enhanced (above 80% increases). Similarly, the in vivo pharmacokinetics parameters also increased, Cmax (from 737.94 to 1117.57 ng × mL(-1)), AUC0- (from 5285.9 to 7409.8 ng × h × mL(-1)) or relative bioavailability (139.38%). The gastric irritation bioassay further showed that the CAP-HP-β-CD was far better than free CAP.

CAP exhibited significant aqueous solubility and oral bioavailability, as well as minimal irritation effect after forming inclusion complex with HP-β-CD. Therefore, these findings could provide an equally important alternative option for the clinical use of CAP.