Solid self-microemulsifying drug delivery system (S-SMEDDS) prepared by spray drying to improve the oral bioavailability of cinnamaldehyde (CA)

Abstract

The aim of this study was to prepare a solid self-microemulsifying drug delivery system (S-SMEDDS) of cinnamaldehyde (CA) by spray drying technique to improve the oral bioavailability of CA. The preparation of CA S-SMEDDS with maltodextrin as the solid carrier, a core-wall material mass ratio of 1:1, a solid content of 20% (w/v), an inlet air temperature of 150 °C, an injection speed of 5.2 mL/min, and an atomization pressure of 0.1 MPa was determined by using the encapsulation rate as the index of investigation. Differential scanning calorimetry (DSC) revealed the possibility of CA being encapsulated in S-SMEDDS in an amorphous form. The in-vitro release showed that the total amount of CA released by S-SMEDDS was approximately 1.3 times higher than that of the CA suspension. Pharmacokinetic results showed that the relative oral bioavailability of CA S-SMEDDS was also increased to 1.6-fold compared to CA suspension. Additionally, we explored the mechanism of CA uptake and transport of lipid-soluble drugs CA by S-SMEDDS in a Caco-2/HT29 cell co-culture system for the first time. The results showed that CA S-SMEDDS uptake on the co-culture model was mainly an energy-dependent endocytosis mechanism, including lattice protein-mediated endocytosis and vesicle-mediated endocytosis. Transport experiments showed that CA S-SMEDDS significantly increased the permeability of CA in this model. These findings suggested that CA S-SMEDDS is an effective oral solid dosage form for increasing the oral bioavailability of lipid-soluble drug CA.

Keywords:

• Cinnamaldehyde
• S-SMEDDS
• Caco-2 cells
• HT29 cells
• uptake

Authors contributions

Xiaoqin Chu, Xiang Li, Ye Cai, and Yun Meng contributed to the experimental design of this study. Yun Meng, Ye Cai and Mengyao Cui performed the experiments. Ye Cai, Yuhang Xu and Long Wu contributed to the acquisition and analysis of data. Yun Meng prepared figures and drafted the manuscript. Xiaoqin Chu and Xiang Li contributed to the study supervision.

Acknowledgments

This work was funded by the National Natural Science Foundation of China (No. 81803831), Anhui Provincial Major Science and Technology Project (201903a07020007) and Major Programs of Natural Science Research in Colleges and Universities in Anhui Province (2023AH040108).

Disclosure statement

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

Data availability statement

Data are available on request.