Self-emulsifying drug delivery systems: Design of a novel vaginal delivery system for curcumin.
OBJECTIVE
The aim of this study was to develop a vaginal self-emulsifying delivery system for curcumin being capable of spreading, of permeating the mucus gel layer and of protecting the drug being incorporated in oily nanodroplets towards mucus interactions and immobilization.


METHODS
The emulsifying properties of curcumin loaded SEDDS containing 30% Cremophor RH40, 20% Capmul PG-8, 30% Captex 300, 10% DMSO and 10% tetraglycol (SEDD formulation A) as well as 25% PEG 200, 35% Cremophor RH40, 20% Captex 355, 10% Caprylic acid and 10% Tween 80 (SEDD formulation B) after diluting 1+2 with artificial vaginal fluid were characterized regarding droplet size and zeta potential. Collagen swelling test was used to examine the irritation potential of SEDDS. Additionally to mucus binding studies, permeation studies in the mucus were performed. Furthermore, spreading potential of the novel developed formulations was compared with a commercial available o/w cream (non-ionic hydrophilic cream) on vaginal mucosa.


RESULTS
SEDDS displayed a mean droplet size between 38 and 141nm and a zeta potential of -0.3 to -1.6mV. The collagen swelling test indicated no significant irritation potential of both formulations over 24h. An immediate interaction of unformulated curcumin with the mucus was determined, whereas both SEDDS facilitated drug permeation through the mucus layer. Formulation B showed a 2.2-fold improved transport ratio of curcumin compared to SEDD formulation A. In comparison to the vaginal cream, SEDD formulation A and B were able to spread over the vaginal mucosa and cover the tissue to a 17.8- and 14.8-fold higher extent, respectively.


CONCLUSIONS
According to these results, SEDDS seems to be a promising tool for vaginal application.
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, 6020 Innsbruck, Austria.
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Köllner
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, 6020 Innsbruck, Austria.
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Nardin
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, 6020 Innsbruck, Austria.
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Markt
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, 6020 Innsbruck, Austria.
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Griesser
University of Innsbruck, Institute of Pharmacy/Pharmaceutical Technology, CCB - Centrum of Chemistry and Biomedicine, Innrain 80-82, 6020 Innsbruck, Austria.
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Prüfert
University of Innsbruck, Institute of Pharmacy/Pharmaceutical Technology, CCB - Centrum of Chemistry and Biomedicine, Innrain 80-82, 6020 Innsbruck, Austria. Electronic address: Andreas.Bernkop@uibk.ac.at.
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Bernkop-Schnürch
D000282:Administration, Intravaginal; D001682:Biological Availability; D002210:Caprylates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry*; D009093:Mucus / Q000378:metabolism; D010316:Particle Size; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D012995:Solubility; D014622:Vaginal Creams, Foams, and Jellies / Q000737:chemistry*
D002210:Caprylates; D045703:Emulsifying Agents; D004655:Emulsions; D011136:Polysorbates; D014622:Vaginal Creams, Foams, and Jellies; C022131:cremophor; D011092:Polyethylene Glycols; D003474:Curcumin; C031492:octanoic acid
Curcumin; Mucus interaction; Mucus permeation; SEDDS; Spreading; Vaginal application