Possibilities of the microemulsion use as indomethacin solubilizer and its effect on in vitro and ex vivo drug permeation from dermal gels in comparison with transcutol®.

OBJECTIVE: Transcutol® is a perfect solubilizer and an effective permeation enhancer of many active substances commonly used in cosmetics. Microemulsions due to the content of surfactant and co-surfactant could be also considered as chemical permeation enhancers that may support transdermal delivery of poorly water- soluble drugs. The purpose of this study was to investigate the effect of Transcutol® and potential microemulsions on diffusion of poorly soluble indomethacin through an artificial membrane and excised rat skin. METHODS: After drug solubilization in different enhancers, drug was dispersed in sodium alginate or carbopol gel used as dermal basis. For characterization of the microemulsions, the basic physico-chemical properties were determined. In vitro as well as ex vivo drug release was determined by vertical Franz cells. RESULTS: Enhancing effect of the examined microemulsions was observed only in carbopol gel. There was an increase in cumulative drug amount released through synthetic membrane by 37.7-39.8% from the microemulsion formulation and 90.6% from Transcutol® formulation within 6 h compared to the control samples. The differences between the permeation curves with or without the content of the enhancers were statistically significant (p < .05). Pearson correlation coefficients indicate a very high degree of dependence (r > 0.9) between in vitro and ex vivo drug release from all dermal vehicles used. CONCLUSION: It can be stated that Transcutol® is the best solubilizer and also penetration enhancer from the examined, and therefore it seems to be effective excipient/solubilizer in topical IND formulation.

In vitro liberation of indomethacin from chitosan gels containing microemulsion in different dissolution mediums.

The objective of this research is to outline the liberation of indomethacin from different chitosan gels containing O/W microemulsion. The influence of surfactant, sodium lauryl sulfate, in two concentrations (0.5% and 0.75%, w/w) was determined in dissolution medium on the release of indomethacin, which was used as poor water-soluble model drug. Chitosan gels were prepared in four different concentrations of chitosan-1%, 1.5%, 2%, and 3% (w/w). Microemulsion enhanced the liberation of the indomethacin from chitosan gels into all dissolution mediums. Adding the surfactant into phosphate-buffered saline decreased the amount of liberated indomethacin from microemulsion, gel mixture, but increased the drug liberation from pure chitosan gels. It was detected that with the increased concentration of chitosan in the samples, the amount of indomethacin liberated (p < 0.05) also increased. A conclusion was drawn that the liberation of indomethacin from chitosan gels was influenced by increased pH of the samples. The high viscosity induced a higher release of indomethacin from 3% (w/w) chitosan hydrogel at pH 5.8 as compared with 3% (w/w) chitosan hydrogel at pH 3.8. The highest percentage of released indomethacin was determined when a mixture of microemulsion gel with higher chitosan content was used.