Vaginal absorption permeability

Possible noninvasive routes for delivery of proteins include nasal, buccal, rectal, vaginal, transdermal, ocular, oral, and pulmonary. For each route of delivery there are two potential barriers to absorption permeability and enzymatic barriers. All of the... 

However, these general observations do not take into account the cyclical changes in the vaginal epithelium, which exert profound effects on vaginal absorption, especially for hydrophilic compounds. The permeability coefficient for the vaginal membrane (Pm) is equal to the sum of the permeability coefficient through the lipid pathway (P ) and the pore pathway (Pp) ... 

The vaginal mucosa permeability of the doe rabbit has been examined by continuous perfusion of straight-chain alkanols and alkanoic acids. Similar to the vaginal absorption of ethynodiol diacetate... 

For the vaginal absorption of ionizable compounds, such as the homologous series of n-alkanoic acids, the apparent permeability coefficient Papp becomes pH-dependent and is defined by Eq. (4) ... 

The cyclic variation in vaginal drug permeability observed in rhesus monkeys in association with the rhythmic pattern of the sexual cycle suggests that the vaginal absorption data generated in the rhesus monkeys may be more reflective of what will occur in humans. The rhesus monkey is, therefore, a good animal model for the research and development of intravaginal delivery devices. 

Fig. 9 Comparison of apparent permeability coefficients, Papp. for the vaginal absorption of straight-chain alkanols in non-cyclic rabbits and cyclic rhesus monkeys. (From Refs. . )...

The surfaee area available for absorption in the buccal mucosa is much smaller than that in the GI, nasal, reetal, or vaginal mucosae. The bueeal mucosa is continuously bathed by saliva whieh reduees the drug concentration at the absorbing membrane. These two faetors, along with the permeability coefficient of the drug, affeet the overall absorption rate of a drug by this route. In addition, the bueeal mueosa is less permeable than any of the above mentioned mucosae. 

A more permeable epithelium obviously facilitates greater absorption. Some epithelia are relatively more permeable than others. For example, the skin is an extremely impermeable barrier, whereas the permeability of the lung membranes towards many compounds is much higher than the skin and is also higher than that of the small intestine and other mucosal routes. The vaginal epithelium is relatively permeable, particularly at certain stages of the menstrual cycle. 

Although, as described above, the vagina is permeable to many peptides and proteins, in most cases the bioavailability is insufficient for systemic therapy and is also highly variable. Penetration enhancers may be used to promote peptide absorption across the vaginal epithelium. However, less extensive investigations on the use of penetration enhancers for the vaginal route have been carried out in comparison to other routes, such as intranasal and transdermal (see Sections 9.7.1 and 8.6.1). 

This article describes the physiology of the human vagina, its characteristics of absorption, and its permeability. The reader will also be familiarized with current research trends in vaginal delivery and absorption of drugs. 

Unlike other tissues, the vagina is greatly affected by steroid replacement therapy. Estrogen replacement therapy is often used to treat menopausal symptoms. The postmenopausal state of the vaginal epithelium, with its thinner epithelium and increased permeability, is an important consideration in drug delivery. The minimization of epithelial fluctuation will result in less fluctuation in absorption, affecting both systemic and local drug deliveries. 

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