Physical model approach in the study of the transport of alkyl amines across a silicone rubber membrane in a two-chamber diffusion cell.

The transport of hexylamine and octylamine through a silicone rubber membrane was studied as a function of buffer (phosphate) concentration and pH. The results were interpreted using a physical model which assumed a steady-state rate of transport and which accounted for the simultaneous diffusion and rapid equilibrium of all the aqueous species, the possible diffusion of both the amine and its protonated form through the membrane, and the effect of a stagnant aqueous diffusion layer on each side of the membrane. The following conclusions were reached: The thickness of the aqueous diffusion layer is approximately 100 micron, which is about the same as that previously measured for benzoic acid in this system.

Quantitative microradiographic study of simultaneous demineralization/remineralization of dental enamel in weak acid buffers.

The remineralization behavior of weak acid-treated bovine tooth enamel has been investigated using a recently developed quantitative microradiographic method. Acetate buffer solutions at pH 4.5 containing calcium, phosphate, and 10 ppm fluoride were used in this study.

Quantitative microradiography for studying dental enamel demineralization and remineralization.

A method for quantitative determination of mineral density changes in dental enamel has been developed. It utilizes the quantitative microscopy capabilities of image analysis or photometer systems. Characteristic demineralization of bovine enamel in acetate buffers containing calcium and phosphate has been used to demonstrate the results.

Synthesis and evaluation of a series of 2'-O-acyl derivatives of 9-beta-D-arabinofuranosyladenine as antiherpes agents.

A series of four 9-(2-O-acyl-beta-D-arabinofuranosyl)adenines (5a-d) was synthesized by acylation of 9-[3,5-bis-O-(tert-butyldimethylsilyl)-beta-D-arabinofuranosyl]adenine (2), followed by removal of the tert-butyldimethylsilyl groups under conditions (HOAc, tetra-n-butylammonium fluoride) that prevented acyl migration. The four 2'-O-acyl derivatives 5a-d showed activity in vitro against herpes type 1 viruses [virus ratings = 1.5-2.

Powder suspension method for critically re-examining the two-site model for hydroxyapatite dissolution kinetics.

A powder dissolution method has been developed, and experiments with the hydroxyapatite suspensions confirm earlier conclusions based on dissolution from hydroxyapatite disks. Although a quantitative assessment of the properties of site 1 was not possible from the data obtained in the present study, a rather accurate and independent evaluation of the properties and the behavior of site 2 of the two-site model for hydroxyapatite dissolution was possible, and the results clearly validate the original two-site model. The present work together with the earlier disk studies show that dissolution from site 2 is well described by a first-order expression, rate = kc2 (Cs2-C), where kc2 is a first-order rate constant, Cs2 is the apparent solubility for site 2 (defined by an ion activity product, KHAP, of the form a10Ca2+PO43-a2OH-, and the solution conditions), and C is the microenvironmental solution concentration of hydroxyapatite.

Correlation of microenvironmental drug concentration with inhibition of growth of microorganisms on surfaces.

Methodologies have been developed to study the concept of microenvironmental drug concentration (C*) near or around microorganisms. C* may be calculated from data on drug release from a depot site by using appropriate diffusion relationships. By following C* and correlating this with the minimum inhibitory concentration (CMIC), one could attempt to predict the effectiveness of an antiplaque agent.

Evaluation of prodrugs of 9-beta-D-arabinofuranosyladenine for therapeutic efficacy in the topical treatment of genital herpesvirus infections in guinea pigs.

Prodrugs of the antiviral agent 9-beta-D-arabinofuranosyladenine (araA), which were more effective than the parent compound in penetrating vaginal membranes in vitro, were synthesized and examined for efficacy in the topical treatment of genital infections with herpes simplex virus type 2 in female guinea pigs. Treatment with 10% araA-5'-monophosphate or 10% araA-5'-monovalerate twice a day for 7 days, starting 6 h after intravaginal inoculation with virus, completely aborted the primary infection. When initiation of treatment was delayed until 24 h postinfection, araA-5'-monophosphate and araA-5'-monovalerate were no longer effective in reducing the mean lesion scores or mean vaginal virus titers.

Solution activity product (KFAP) and simultaneous demineralization-remineralization in bovine tooth enamel and hydroxyapatite pellets.

The effects of changing the ion activity product of the remineralization solution at pH 4.5 (pKFAP 108-118) on the remineralization behavior of demineralized bovine tooth enamel and hydroxyapatite pellets have been studied. Solutions containing calcium-4.

Topical vaginal drug delivery I: effect of the estrous cycle on vaginal membrane permeability and diffusivity of vidarabine in mice.

Preliminary studies showed that the vaginal membrane permeability coefficients for vidarabine (9-beta-D-arabinofuranosyladenine) varied widely within a group of mice of the same species and age. This finding prompted an investigation of the influence of the female mouse sexual cycle on the vidarabine permeability. By means of a vaginal smear technique, the sexual cycle, which was approximately 5 days in duration, was divided into five phases.

Permeation of skin and eschar by antiseptics II: influence of controlled burns on the permeation of phenol.

The safe antiseptic use of phenol over the burn-traumatized surface depends on knowledge of how the systemic accumulation of phenol is affected by burn processes. To gain insight into the underlying permeation phenomenon, the diffusion of phenol and a reference cosolute, methanol, through both scalded and branded dorsal skin sections of the hairless mouse was studied as a function of burn temperature using in vitro diffusion cells. Temperatures up to 100 and 150 degrees were used for scalding and branding, respectively, using a 60-sec; exposure time.

Permeation of skin and eschar by antiseptics I: baseline studies with phenol.

To assess how the permeability of phenol is altered by thermal injury, it was first necessary to have baselines of comparison on normal skin. Using in vitro diffusion cells and the skin of the hairless mouse, [14C]phenol was applied to skin in an aqueous medium with a reference copermeating species, [3H]methanol, and 37 degrees permeability coefficients of the pair were evaluated as functions of animal age, skin hydration, stripping of the skin, dermis isolation, and phenol concentration. Age proved to be of little consequence to permeability over a wide age range.

Hydration and percutaneous absorption III: Influences of stripping and scalding on hydration alteration of the permeability of hairless mouse skin to water and n-alkanols.

The influence of hydration on the permeability of stripped and scalded skins of hairless mice was investigated in vitro using water and n-alkanols as test permeants. Irrespective of pretreatment, the permeation rates of water, methanol, and ethanol were unaffected by aqueous immersion of skin sections in a diffusion cell, consistent with earlier data on unprocessed skins. The permeation rates of butanol and hexanol also were insensitive to hydration, differing from earlier studies on normal, intact skin in which both solutes' rates doubled after 10 hr of soaking.

Influence of benzalkonium chloride on the dissolution rate behavior of several solid-phase preparations of cholesterol in bile acid solutions.

Cholesterol dissolution rate accelerators, such as benzalkonium chloride, function by reducing the interfacial barrier that exists between the negatively-charged bile acid micelle and the negatively-charged cholesterol surface. It has been proposed that this reaction is accomplished by the binding of the positively-charged accelerator to the negatively-charged micelle. An earlier report showed that different solid preparations of cholesterol give different dissolution rates under the same conditions and these differences can be primarily accounted for by variations in the interfacial transport constant (P).

Permeability of thermally damaged skin v: permeability over the course of maturation of a deep partial-thickness wound.

The permeability of eschar is an important factor governing rational approaches to topical control of burn wound sepsis. Previous work has shown the burn wound to have a highly variable permeability immediately after burning depending on the manner of burning. But the burn is also a dynamic wound and its physical state changes during the process of maturation.

Theoretical and experimental studies of transport of micelle-solubilized solutes.

A physical model describing the simultaneous diffusion of free solute and micelle-solubilized solute across the aqueous boundary layer, coupled with partitioning and diffusion of free solute through a lipoidal membrane, is derived. In vitro experiments utilizing progesterone and polysorbate 80 showed excellent agreement between theoretical predictions based on independently determined parameters and experimental results. The physical model predicts that micelles can assist the transport of solubilized solute across the aqueous diffusion layer, resulting in a higher solute concentration at the membrane surface than would be predicted if micelle diffusion is neglected.

Delivery of liposome membrane-associated sterols through silastic membranes.

The transport of sterols incorporated into the lecithin bilayer of small unilamellar liposomes through a model membrane was studied. A two-chamber diffusion cell containing liposomes with incorporated [4-14C)cholesterol or beta-[4-14C]sitosterol in the donor chamber and liposomes with unlabeled cholesterol in the receiver chamber was used. The permeability coefficients of the sterols through silastic rubber membranes which served as a model membrane were measured.

Novel topical fluoride delivery system II: remineralization of human teeth.

A recently conceived calcium fluoride-containing remineralization system was tested using human teeth in vitro. The influence of several variables (surface pretreatment, demineralization time, and remineralization time) was studied. Appreciable levels of fluoride taken up by pumiced human teeth were found at depths up to 50 micrometers when remineralization was carried out in either the remineralizing solution or saliva.

Novel topical fluoride delivery system I: remineralization of ground bovine teeth.

Laboratory studies were carried out on a newly conceived fluoride-containing remineralizing system with bovine teeth. The prototype fluoride delivery device involved micronized calcium fluoride maintained at the tooth surface with a cellulose film. Together with salivary calcium and phosphate (or simulated saliva), this system was able to generate and maintain the appropriate thermodynamic activity driving force for significant fluorapatite deposition in a reasonably short time (approximately 48 hr).

Fluoride remineralization of demineralized bovine tooth enamel and hydroxyapatite pellets.

Both bovine enamel and hydroxyapatite pellets were remineralized in a fluoride-containing remineralization solution after prior demineralization for various lengths of time. In both the enamel and pellet systems, the degree of remineralization attainable was directly related to the extent of prior demineralization, although the demineralized material was never 100% recovered in remineralization. In some cases, fluoride levels up to several thousand parts per million were found at depths as great as 50 micrometers from the surface.

Variability in dissolution rates of cholesterol pellets in bile acid solutions.

Large variations in dissolution rate behavior of cholesterol monohydrate pellets may result from small changes in experimental procedures. For example, when cholesterol monohydrate pellets were stored overnight prior to a dissolution run, the initial dissolution rates varied by more than a factor of 2. It is well known that cholesterol monohydrate is converted to anhydrous cholesterol; cholesterol may be unstable toward light.

Dissolution rate behavior of solid cholesterol preparations in bile acid solutions.

Recent work in these laboratories showed that different preparations of cholesterol monohydrate and anhydrous cholesterol had different dissolution rates under the same conditions. A method was developed by which both the thermodynamic contribution (Cs) and the interfacial kinetic contribution (P) to dissolution could be determined from experimental data. The rotating-disk dissolution method was used with the Levich theory to assess the data.