Intravaginal Drug Delivery Systems

Within recent years the level of interest in both local and systemic vaginal drug delivery systems has increased considerably. The vagina offers numerous advantages as a site for drug delivery, such as convenient access, prolonged retention of formulations, a great permeation area, high vascularization, relatively low enzymatic activity, and the avoidance of first-pass metabolism. The development of novel products for female health, comprising therapeutic substances such as peptides, proteins, antigens, or antisense oligonucleotides, necessitates the design of high performance intravaginal drug delivery systems. In the case of local treatment, it is challenging to design delivery systems providing high drug concentrations in the vagina for a prolonged period of time, while in the case of systemic treatment, the major challenge is to gain high drug bioavailabilities. On the basis of knowledge of the relevant anatomical and physiologic features of the vagina, and on the fate of vaginal drug delivery systems after application, various auxiliary agents have been developed for vaginal use. They include permeation enhancers, such as bile salts, benzalkonium chloride, or palmitoylcarnitine chloride, solubility-enhancing agents, such as cyclodextrins, and enzyme inhibitors such as glycocholate, aprotinin or edetic acid (EDTA). Furthermore, multifunctional polymers exhibiting bioadhesive and/or in situ gelling properties, such as thiolated polyacrylates and poloxamer, represent useful tools for the design of vaginal drug delivery systems. Dosage forms comprising such auxiliary agents include vaginal tablets, inserts, microparticles, vaginal rings, suppositories/pessaries, hydrogels, creams, and liquid formulations. Vaginal administration of drugs, which are specifically used for the treatment of osteoporosis, hormone replacement therapy, contraception, infections, infertility, and other female-related conditions, is a feasible alternative to oral or parenteral administration.