Zhang Yong1, Wang Xingqi1, Huang Jie1, Hu Rongfeng1, Chu Xiaoqin1,2. 1. Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China. 2. Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, China.
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 Tmax 60 min, Cmax 1063.41 mg/L, AUC0-∞ 113102.61 mg/L*min, respectively. Tmax, Cmax, and AUC0-∞ 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.
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 Tmax 60 min, Cmax 1063.41 mg/L, AUC0-∞ 113102.61 mg/L*min, respectively. Tmax, Cmax, and AUC0-∞ 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.
Entities:
Keywords:
Box–Behnken design; CA-SME; formulation; in vitro release; pharmacokinetic evaluation; production optimization