Preparation, characterization and pharmacokinetics of Cucurbitacin B solid dispersion

Abstract

Cucurbitacin B (CuB) is a type of tetracyclic triterpenoids derived from the Cucurbitaceae melon, which has various biological activities. However, the poor water solubility and low bioavailability of CuB limit its wide range of clinical applications. Objective: The present study aimed at the preparation of CuB to increase its solubility and further improve the oral bioavailability by using solid dispersion system (SD). Methods: The optimal carrier was screened by crystallization inhibition and solubility test, and CuB-SD was further prepared by the solvent method. The optimal formulation was screened using dissolution as an indicator and characterized by techniques like DSC, XRPD, FTIR and SEM. The pharmacokinetic study was conducted to explore the potential of CuB-SD for oral administration. Results: From the dissolution study, the cumulative dissolution of CuB prepared by the solvent method was nearly 6 times higher than the CuB. Moreover, DSC, XRPD and SEM analyses indicated that partial transformation of CuB into an amorphous form in SD formulations. FTIR demonstrated that there was hydrogen bonding between CuB and the carrier, which supported the higher solubility and dissolution of the CuB-SD. The in vivo pharmacokinetic study, UPLC-MS/MS was used to measure the concentration of CuB in plasma. In vivo study indicated that the formation of CuB-SD could largely improve the absorption of CuB, the AUC0-24h of CuB-SD (1:7) formulation was 3.6-fold higher than pure CuB. The AUC0-∞ of CuB-SD (1:7) was 692.44 ± 33.24 (ng/mL)*h, which was 498.77 ± 26.27 (ng/mL)*h and 187.41 ± 10.41 (ng/mL)*h for CuB-SD (1:5) and CuB, respectively. Conclusions: Collectively, CuB-SD was a promising way to enhance the oral bioavailability of CuB.

Keywords

• Cucurbitacin B
• Solid dispersion
• Dissolution rate
• Pharmacokinetics
• Bioavailability
• Solvent method