Comparative dissolution studies for the drugs showing low solubility
Project no. 1125 · Status: Kapanmış · 2018
Summary
The aim of this Project is to develop a new ovule formulation containing Nystatin and Nifuratel concomitantly and compare in-vitro dissolutions and the permeabilities of this formulation with the reference product which is commercially available. In the scope of the conducted project, the solubility studies of Nystatin and Nifuratel, indicated for the multifunctional treatment of vulvovaginal diseases caused by pathogenic microorganisms (Candida, Trichomonas and the bacterias) and whose in-vivo assays cannot be performed likewise in several ovule formulations, have been performed to determine the medias for in-vitro dissolution assays and the content of the formulation and the in-vitro dissolution assays have been performed for the ovule containing the active ingredients concomitantly by classical dissolution method. Also in-vitro permeability assays were performed with HEC-1A cell line. Firstly; a determination method was developed with high pressure liquid chromatography (HPLC) and this method was validated. Following validating the method, the solubility assays were performed in different medias with an appropriate pH for vagina to determine the optimal media that would be used for in-vitro dissolution studies. The in-vitro dissolution assays were conducted with the chosen different medias. Moreover, a solubility assay for the content of the formulation’s matrix was also performed. Two new formulations were developed and the one with the optimal results was chosen as our final formulation. According to the results obtained from the conducted studies it has been experienced that Nystatin and Nifuratel cannot be released exactly even in the medias that they show optimal solubility and the sink conditions cannot be maintained because of the active ingredients low solubility and the content of the formulation. Since in-vitro release cannot be shown, in-vitro permeability assays were performed with HEC-1A cell line. As a result of the performed assays, it has been concluded that dissolution studies for the ovules showing low solubility will not be a good option because of the low dissolution profile but the in-vitro comparison can be possible with permeability assays conducted with cell cultures and cell lines.