Formulation, production, in vitro release and in vivo pharmacokinetics of cinnamaldehyde sub-micron emulsions

Abstract

Objective: The purpose of this study was to study the effects of formulation of cinnamaldehyde submicron emulsion (CA-SME) and optimize the preparation process parameters of CA-SME, characterize CA-SME and study on in vitro release kinetics and in vivo pharmacokinetics.

Methods: Single factor methodology was used to screen the formulation of CA-SME. Response surface methodology combined with Box–Behnken design (BBD) was used to optimize the process variables of CA-SME. The dynamic dialysis method was used to investigate the in vitro release of CA from CA-SME. The blood concentrations of CA in rats were measured after oral administration of CA-SME, with CA solution as reference.

Results: The optimal formulation of CA-SME was as follows: 2.5% CA + 1.5% Tween-80 and Span-80 (1:1)+1.5% medium chain triglyceride (MCT)+1.5% Poloxamer-188 + 1.5% lecithin + 91.5% ultrapure water. With the entrapment efficiency (EE/%) of CA-SME as index, BBD experiments indicated that the optimum emulsification temperature, homogenization pressure and cycles were 56 °C, 52 MPa, and two cycles, respectively. The mean particle size and EE of optimum CA-SME were 257.23 ± 3.74 nm and 80.31 ± 0.68%, respectively. The in vitro release study exhibited that the release kinetics of CA-SME was first-order model. Pharmacokinetic parameters of CA-SME in rats were T_max 60 min, C_max 1063.41 mg/L, AUC_0–∞ 113102.61 mg/L*min, respectively. T_max, C_max, and AUC_0–∞ of CA-SME were 3, 3.5, and 2.3 times higher than that of CA solution, respectively. The pharmacokinetic parameters of CA-SME in rats were significantly higher than those of CA solution. Submicron emulsion shows great potential as delivery strategy for this volatile herbal oil in oral administration.

Keywords:

• CA-SME
• formulation
• production optimization
• Box–Behnken design
• in vitro release
• pharmacokinetic evaluation

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Acknowledgements

The authors express special thanks to Dr. Xiaoqin Chu for useful communication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors gratefully acknowledge support from the National Natural Science Foundation of China [Nos. 81803831 and 81973488], Anhui Provincial Talents Project for youth in Universities [No. gxyq2018025].