Formulation, characterization, and in-vivo evaluation of Zaltoprofen self-microemulsifying drug delivery system

Abstract

Purpose

2-(10,11-Dihydro-10-oxodibenzo [b,f] thiepin-2-yl) propionic acid (Zaltoprofen) is classified as a BCS class II anti-inflammatory drug, having low solubility and less bioavailability.

Methods

This study describes the development and characterization of self-micro emulsifying drug delivery system (SMEDDS) of the poorly water-soluble compound Zaltoprofen that resulted in improved aqueous solubility, dissolution, and in-vivo oral absorption. The solubility of Zaltoprofen was determined in various vehicles, including oils, surfactants, and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for Zaltoprofen formulations contained 80% mixtures of surfactant:co-surfactant Labrasol:Cremophor RH 40 (4:1), and 20% of oil, ethyl oleate. Further, SMEDDS was characterized by particle size, zeta potential, dissolution studies, and anti-inflammatory activity.

Results

The Zaltoprofen-SMEDDS rapidly formed fine oil-in-water microemulsion, which was thermodynamically stable, having an average particle size of 451.3 ± 3.2 nm. The in-vitro dissolution rate of Zaltoprofen from SMEDDS was significantly higher (p<.01) compared to marketed tablets in 0.1N HCL and pH 4.5 buffer. SMEDDS showed highly significant inhibition (p<.01) of inflammation in rat paw edema compared to the drug.

Conclusions

The study demonstrated that the self-micro emulsifying system poses a promising strategy for developing hydrophobic compounds with low oral bioavailability.

Graphical Abstract

Keywords:

• Pharmacodynamic activity
• pseudo ternary diagram
• Zaltoprofen SMEDDS

Acknowledgments

The authors would like to acknowledge Ms. Pooja Bakshi for drafting the manuscript. We would also like to acknowledge IPCA Laboratories, India, for providing the gift sample of Zaltoprofen and Gattefosse Pvt. Ltd., India, for providing the gift samples of excipients.

Disclosure statement

The authors do not have any conflict of interest to declare.