Clotrimazole (CT), which is an imidazole derivative, is widely and effectively used for the treatment of vulvovaginal candidiasis.1) Unfortunately, oral use of CT is unacceptable due to the severe side effects. Thus, topical administration of CT is recommended. However, it is limited by its very low water solubility resulting in the essential to incorporate CT into a suitable vehicle. Commercially conventional CT vaginal delivery systems, such as creams, foams, and gells, are considered to reside for a relatively short period of time at the targeted site. The entrapment of drug in vesicles is viewed to help in the localized delivery of the drug and an improved solubility and availability of the drug at the site will reduce the dose.As can be known, liposomes are starting to be widely investigated in topical applications for the skin, 2-4) oral 5) and vaginal diseases. 6,7) Liposomes have been shown to enhance the penetration of vesicle-bound-drugs into the skin, after topical application, acting as a "drug localizers," with low systemic absorption of the drugs, in comparison to other galenical formulation, resulting in less drug side-effect and sustained drug releasing.
2)But liposomes still have physical stability problems associated with the aqueous suspension such as aggregation, fusion limit their shelf life. Concern on these problems, these stability problems can be avoided by formulating liposomes as proliposomes. Proliposomes are dry, free-flowing products, which, on addition of water, disperse to form a liposomal suspension.8) Thus, it can be fabricated in various dosage forms including tablets and capsules which were more convenient for vaginal administration than liposomes solution. In addition, proliposomes have a number of advantages over liposomes. For example, they tolerate sterilization by ultraviolet and are much more stable physicochemically. Proliposomes offer a versatile liposomes delivery concept with potential for use with a wide range of active compounds and various drug administration routines. [9][10][11][12][13][14][15] In present study it was to investigate the feasibility of proliposomes to formulate the vaginal administration of CT. Proliposomes are formed by penetrating organic solution of CT and phosphatidylcholine (PC) into microporous sorbitol particles, followed by vacuum evaporation of the solvent method. Formulations composed of egg phospholipid, cholesterol compositions have been characterized by encapsulation efficiency. In addition, we are investigating the optimized resultant liposomes in vitro release study. Furthermore, we describes an attempt to achieve the antifungal activity more efficiency followed by a prolonged delivery of CT via a vaginal application of appropriate dosage forms of CT. A physical mixture of CT and sorbitol was also prepared and compared for antifungal efficiency with proliposomes following vaginal application in rats. Further, proliposomes system was evaluated by tolerability on tissue level in rat.
ExperimentalMaterials Clotrimazole (CT) and Egg ph...