Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate

Abstract

Purpose:

The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability.

Materials and methods:

The optimized liquid SMEDDS was composed of castor oil, Tween^® 80, and Plurol^® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder.

Results:

The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and C_max were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions.

Conclusion:

This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.

Keywords:

• methotrexate
• solid SMEDDS
• solubility
• bioavailability
• photostability

Acknowledgments

This work was supported by the National Research Foundation (NRF) of South Korea grants funded by the South Korean government (MEST) (No. 2018R1D1A1B07050598). This paper was presented at the 2018 PharmSci 360 as a poster presentation with interim findings.

Disclosure

The authors report no conflicts of interest in this work.