Characterization of Self-Emulsifying Drug Delivery Systems Using In Situ Raman Spectroscopy to Study the Precipitation Inhibition Mechanism of Poorly Water-Soluble Drugs

Purpose

The goal of this research was to study the molecular interactions in situ between actives and surfactants in self-emulsifying delivery systems (SEDDS) in order to illuminate the factor(s) and how they influence the drug performance in these systems.

Method

We have developed an approach to evaluate the mechanism of performance of SEDDS formulations using an in situ Raman technique. Self-emulsifying delivery systems for seven actives with different physicochemical properties were formulated. One gram of the SEDDS was dispersed in 100 mL of media, and the precipitation behavior of the actives was noted. Using an immersion probe, these dispersions were tested continuously and spectra were obtained to determine the drug-excipient interactions.

Results

The changes in the molecular vibrational peaks confirmed that the drug-TPGS hydrogen bonding was responsible for maintaining the drug in solution. The interaction between Labrasol and the actives was weak and broke upon dispersion leading to precipitation of the drug. Also, the hydrogen bond donor strength of the functional group gave a good indication of the bond strength between TPGS and the drugs which determined the performance of the actives in the system.

Conclusion

It could be suggested that the hydrogen bond strength correlates well to the precipitation behavior from the SEDDS dispersions. Thus, studying the structures and physicochemical properties of the drug candidates and the excipients could significantly minimize the steps involved in developing successful lipid-based delivery systems.