Studies On Nystatin In Situ PH-sensitive Gel For Vaginal Use

Vaginal drug delivery system has a long history, and its applications are mainly usedfor the topical treatment of gynecological diseases and vaginal contraceptive. Vaginaltopical administration is superior to oral administration, therefore it is subject to thepharmaceutically attention of researchers because of its high local concentration,antibacterial effect, low toxicity. For women, vaginal preparations have unique use andtherapeutic effect. In situ forming vagina gel is the vaginal preparations administered ina liquid state, occuring in the administration site after the phase transition, the formationof the semi-solid gel state of the non-chemical crosslinking. The transfer systemcombines the advantages of the solution with the gel formulation, the carrier particularlysuitable for topical administration. This article select Nystatin (NYT) as a model drug,hydrophilic polymer material prepared pH-sensitive vaginal gels, the text of whichreads as follows:In the preformulation study work, this article established determination of UVspectrophotometry for the basic physical and chemical properties of NYT, and NYToil-water distribution coefficient was determined.By screening the pH-sensitive matrix Carbopol980NF, compatibility selectpolyvinyl alcohol series and poloxamer series matrix to inspect and ultimately preferredCarbopol980NF and PVA-203as a pH-sensitive gel matrix, the viscosity of theirconcentration solutions was measured, and Conducting the Study of Single factors forthe main drug, glycerol, Nepal methylparaben. With gelling viscosity as a criteriondetermining the optimal prescription by Star Dot Design-response surface optimizationmethod, the optimal prescription of the experiments was obtained: Nystatin0.9%,Carbopol980NF0.655%, PVA-2031.213%, Glycerin10%and Methylparaben0.09%.Under non-physiological conditions(pH3.80, T25℃) the preparation had a smallviscosity, free-flowing, easy to be injected into the vagina; under physiologicalconditions(pH4.00, T37.5℃) occurring phase transition and becoming a semi-solid gel, by the response of the pH in the vagina to form a stronger gel under pathologicalconditions(pH4.60, T37.5℃).According to the vaginal topical administration in vivo characteristics, using thedialysis bag method, the improved slurry method and no film dissolution model, weexamined the dissolution of the gel and drug release behavior. The results showed thatthe drug release being mainly affected the pH-sensitive gel dissolution controlling, andfollowed zero order kinetics process. The cumulative release of the drug showed a goodlinear relationship as the cumulative dissolution amount of gel, both carried out in asimilar rate. The increases of the oscillation frequency and the release area could beincreased gel dissolution and drug release rate. The drug release of NYT pH sensitivehydrogel be presented the phenomenon of diffusion and dissolution coexist, was amixed drug release mechanism.By pH-sensitive vaginal gels preliminary stability and irritating research,the resultsshowed that the formulations be more stable under the conditions of the cryogenicplaced, stable in high temperature, be avoided high temperature and long-termplacement. The formulations prolonged the residence time of the drug in the vagina, andno stimulating effect on rat vaginal, to achieve the intended purpose.Using the rats self-control, high-performance liquid chromatographic method wasdetermined the nystatin concentration-time curve in the vaginal washing liquid, andconducted the study of pharmacokinetic behavior in the vagina for NystatinpH-sensitive in situ gel, vaginal gel and commercially available effervescent. Theresults be showed that the formulation extending the residence time of the drug in thevagina, the average residence time was1.74times and1.64times more than ordinaryeffervescent, having a good application prospect on vaginal drug delivery system.