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.

Permeation of indomethacin from semisolid preparations through various semipermeable membranes.

OBJECTIVE: The aim of this study was to evaluate and compare the permeation of model drug indomethacin (IND) from various types of gels through several semipermeable membranes. METHODS: Permeation of IND from gels based on carbomer (CA), hydroxyethylcellulose (HEC), and polyacrylamid/laureth-7/isoparaffin was performed via diffusion cell method through membranes: shed snake skin, full thickness chicken skin, mucosa of pork small intestine, and cellophane. RESULTS: The least permeation of IND was observed in the case of shed snake skin and full thickness chicken skin. It did not exceed 5.4% of original amount in the preparation after 3 h of measurement regardless the type of gel. In the case of mucosa of pork small intestine and cellophane the permeated amount of IND ranged from 9.4 to 55.4% depending on the type of gelling agent used. There was also quite a significant influence of a gelling agent on the permeation of IND observed. The permeation of IND was highest from CA gel, where it ranged from 0.6 to 52.2% of original amount in the preparation depending on the type of membrane used. Gelling agent inhibiting the permeation the most was HEC, where the permeated amount of IND did not exceed 12.3% regardless the type of membrane used. CONCLUSIONS: In general the permeated amount of IND through biological membranes containing stratum corneum represented just a small part of the amount in original preparation. Gelling agent has significant effect on the extent and rate of permeation.