Derek H. Owen

A vaginal fluid simulant

A fluid medium was developed to simulate the fluid produced in the human vagina. The composition of the medium was based on an extensive review of the literature on constituents of human vaginal secretions. In choosing the ingredients for this medium, the goal was to emphasize properties that influence interactions of vaginal fluid with topical contraceptive, prophylactic, or therapeutic products. Among these properties, pH and osmolarity play a dominant role in physicochemical processes that govern drug release and distribution.

Rheological properties of contraceptive gels

The rheological properties of 4 commercially available contraceptive drug delivery gels and their dilutions with a vaginal fluid simulant were measured. These properties govern the critical functions of spreading and retention of these gels over the vaginal surfaces. Measurements made on Conceptrol, KY Plus, Gynol II, and Advantage-S included stress growth, stress relaxation and residual stress, and the shear rate dependence of viscosity. All gels exhibited non-Newtonian behavior including shear thinning and viscoelasticity. Conceptrol and Gynol II had no residual stress, while both KY Plus and Advantage-S did. The gels differed in their response to dilution with vaginal fluid simulant.

Effect of temperature and pH on contraceptive gel viscosity

The rheological properties of four commercially available spermicidal gels (two polyacrylic acid derivatives and two carboxymethylcellulose based) and their dilutions with a vaginal fluid simulant (pH 4.2) and a semen simulant (pH 7.7) were measured at 25 degrees C and 37 degrees C over a biologically relevant range of shear rates. All four gels were shear thinning with temperature-dependent rheological properties. The two types of gels responded differently to dilution. The rheological properties of the polyacrylic acid derivative gels were strongly dependent on the type of diluent used. Their viscosities after dilution with the semen simulant were 100 times greater than after comparable dilutions with the vaginal fluid simulant, this effect being due primarily to the higher pH. The cellulose gels did not exhibit such an effect. These results suggest that the polyacrylic acid and cellulose gels interact differently with the vaginal environment in vivo. Such differences could lead to differences in the extent and durability of epithelial coating.

Comparison of the rheological properties of Advantage-S and Replens.

The rheological properties of Advantage-S and Replens were measured at body (37 degrees C) and room temperature (25 degrees C) over a range of physiologically relevant shear rates. The viscosity of Replens was found to differ from that of Advantage-S, particularly at room temperature. In addition, the two materials differed in their miscibility with a vaginal fluid simulant.

Applications of biomedical engineering in reproductive biomedicine: sensing and drug delivery to the lower female reproductive tract

Current intravaginal products for contraception and prophylaxis against sexually transmitted diseases lack the efficacy that is both needed and technically possible. A multidisciplinary effort-that integrates gynecology, pathology, microbiology, and reproductive biology with engineering and materials science-can provide critical and missing information to the process of design and development of better products. Several engineering sub-disciplines can contribute to this effort, including electrical, mechanical and chemical engineering. Specific contributions will pertain to the polymeric delivery vehicles for drug delivery, the active ingredients of those vehicles, and to methods of testing, both in vitro and in vivo.

Drug delivery to the lower female reproductive tract: mechanics and surface phenomena

Summary form only given. Drug delivery gels are currently applied to the human vagina for contraception and therapy (e.g. treatment of vaginitis; hormone replacement). An important future application will be prophylaxis against sexually transmitted diseases. Current intravaginal contraceptive products lack the efficacy that is both needed and technically possible. This may derive from inadequate distribution of formulations within the vagina, rather than the potency of their active ingredients per se. While there is much current research on improved active ingredients, little critical scientific attention has been devoted to design of the polymeric vehicles for delivering these ingredients. The vaginal surface consists of contiguous moist epithelium which contains small corrugations (rugae, of length scale 1 mm) and/or layers of mucus or other fluids. Mechanical and chemical interactions influence spreading over these surfaces, retention/adhesion to them, mixing with ambient fluids, and exchange of biologically active molecules from delivery gels to such surfaces and fluids - all functions critical to the performance of intravaginal formulations. Surface phenomena influence all these functions. There is great opportunity to utilize the rational analysis of such phenomena in the design of improved formulations. An understanding of deployment mechanisms can be developed by combination of experimental simulations of sub-processes with fundamental theory of the fluid and solid mechanics of those sub-processes. Measurement of material properties of vaginal formulations provides input data to the theoretical models.