Critical concentrations in the dilution of oral self-microemulsifying drug delivery systems

Abstract

Background: Self-microemulsifying drug delivery systems provide a key technology to formulate challenging drugs. These formulations are commonly screened in early development by simple in vitro dilution tests. However, there is often a lack of rationale of how these tests are performed; so this article aims to improve this situation by studying critical concentrations in the dilution of self-microemulsifying formulations. Methods: Dynamic laser light backscattering, conductivity measurements, and electron paramagnetic resonance spectroscopy were conducted. Results: All model formulations exhibited profound changes at a similar aqueous dilution, which was interpreted as a percolation threshold of the formulation in water. It marked the change of a bicontinuous microemulsion to discrete micelles. The systems exhibited at this point maximal particle dispersion with a threshold of polydispersity. A marked change was also observed in the paramagnetic resonance spectra and with the conductivity measurements. This altered microenvironment can be relevant for solubilized drugs. Conclusions: Future dilution tests should include a formulation-to-water ratio of roughly 1:5 (w/w), which is in the proximity of the individual threshold concentration. Additional dilutions may be tested below and clearly above this value to reflect the physiological dilution process.

Keywords:

• Critical concentration
• dilution
• drug delivery systems
• electron paramagnetic resonance
• percolation theory
• self-microemulsifying

Acknowledgments

The authors thank the University of Applied Sciences Northwestern Switzerland for funding the research project.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.