Anthony J. I. Ward

Microemulsions as topical drug delivery vehicles: in‐vitro transdermal studies of a model hydrophilic drug

Abstract— Microemulsions with a 58:42 weight ratio of dioctyl sodium sulphosuccinate: octanol and containing 15, 35, and 68% water have been tested for their ability to transport glucose across human cadaver skin. A flow‐through multisample skin diffusion cell showed that both the 35 and 68% water microemulsions caused enhanced (approximately 30‐fold) transport of glucose. No transport was discernible for the 15% water microemulsion. Differences in percutaneous glucose transport were shown to parallel differences in the diffusion of water within the microemulsion vehicles before application to the skin.

Pendant drop studies of adsorbed films of bovine serum albumin: I. Interfacial tensions at the isooctane/water interface

Abstract Interfacial tensions, γ, between isooctane and aqueous solutions of bovine serum albumin (BSA) have been studied using the pendant drop method. Constant values of γ were reached after about 60–90 min in the pH range 4–10, and are independent of bulk protein concentration above 0.01–0.04%. The processes by which films at thermal equilibrium were obtained are analyzed in terms of diffusion and segmental adsorption and rearrangement processes. At low pHs (

Microemulsions as Topical Drug Delivery Vehicles. I. Characterization of a Model System

AbstractThe microemulsion region formed by the water/octanol/dioctyl sodium sulfosuccinate (DSS) was characterized by determination of the phase boundaries, water self diffusion coefficients, and in vitro transdermal permeation for radiolabeled water. The 58:42 ratio of DSS:octanol can incorporate greater than 70% water. It is found that the average self diffusion values for water increase ten-fold as the water content increases from 15 to 58% by weight. Values for normalized in vitro transdermal flux of water from the microemulsion showed a similar trend increasing five-fold over the same water content range. This study shows that delivery of the polar water portion of this microemulsion system is highly dependent upon the composition of the microemulsion.

Preparing Narrow Size Distribution Particles from Amphiphilic Association Structures

Small inorganic particles with a narrow size distribution have been prepared from aqueous and organic solutions under varied temperatures, pressures, and concentrations. This article reviews the preparation of such particles from microemulsions and liquid crystals and shows how these amphiphilic association structures can have a pronounced influence on the size, shape, and even chemical composition of the precipitated particles. Surfactants associate in the presence of water to form micelles and lyotropic mesophases. This is a consequence of the molecular geometrical packing requirements, superposed on the dissolution behavior of these substances. Associated structures that have shapes with the lowest free energy are preferentially formed. A balance is attained between the interactions of the hydrophobic portions of the surfactant, reducing the unfavorable contact with aqueous environs and the interactions between the headgroups. The composition regions of these different phases have been widely studied. Micelles exist as normal and reversed structures (Figure 1), while the liquid crystalline phases show a variety of structures which have been studied in great detail. Figure 1 gives a simplified example of the structural conditions in different parts of a phase diagram of the three components water/surfactant/amphiphilic substance (e.g., medium chain length alcohol). The interaction between water and the surfactant is sufficiently pronounced to permit the formation of reversed micelles. The association structures of different regions shown in Figure 1 include normal (L 1 ) and reversed micelles (L 2 ). The hexagonal phase (E) consists of a hexagonal array of cylinders with the hydrocarbon chains situated in the center of the cylinder, while the reverse hexagonal phase (F) is built of cylinders with aqueous centers. The lamellar phase (L α ) is made up of infinite sheets of bimolecularly arranged surfactant molecules separated by aqueous layers. The physical properties and reasons for the formation of such lyotropic phases have been discussed extensively.

Order of Polyoxyethylene Chains in the Lamellar Phase of a Nonionic Surfactant

Abstract Lamellar samples of aqueous tetraethylene glycol n-dodecyl ether in varying degrees of selective deuteration were studied by 2H NMR spectroscopy. Order parameter profiles for both the alkyl and oxyethylene head group chain have been obtained. A maximum in the order of the surfactant molecules was found to occur 3-4 methylene segments from the alkyl/headgroup interface on the alkyl chain. Order decreased rapidly with position on either side of this region giving an approximately symmetrical profile.

The lamellar phase of the sodium dodecylsulfate/decanol/toluene/formamide system: NMR and phase studies of solubilization

The phase behavior of the system sodium dodecylsulfate/decanol/toluene/ formamide was investigated and pseudo-ternary diagrams established. In particular, the effect of varying the amount of toluene in the system on the stability of the lamellar phase region was studied in detail. Deuterium NMR and low-angle x-ray diffraction measurements showed that more toluene was distributed between the surfactant chains as the amount of decanol in the system is reduced, resulting in a more disordered dynamic structure in the bilayers. Similarly, increased formamide content lead to greater penetration of the toluene into the bilayer and more disorder. Both factors were found to be instrumental in decreasing the stability of the lamellar structure.

Molecular interactions in a nonaqueous catanionic system

Abstract The system octanoic acid, octylamine, and formamide were studied with regard to phase equilibria and intermolecular interactions using IR and NMR spectroscopy. The results showed several molecular compounds forming in the formamide-less part of the system. These aggregates did not give rise to association structures of colloidal size with added formamide. The phase equilibria were extremely slow to reach the final positions; 3 weeks of storage was required for the final appearance of the phase diagram.

The use of associated surfactant media for the synthesis of fine particles: Preparation of iron oxides

Abstract Precipitation of iron oxide in a lyotropic liquid crystal medium is compared to that in homogeneous solution. Results indicate that the aqueous layers of the lamellar phase influence both the nucleation and particle growth stages of particle formation. The formation of β-FeOOH occurs in the temperature range 60–90°C. Particle sizes in the range 1–100 nm, depending on the heating times, with needle like morphology are formed.

SOLUBILIZATION OF NONPOLAR OILS IN AQUEOUS MICELLAR MIXTURES OF IONIC AND N0N10NIC SURFACTANTS

ABSTRACT Rates of solubilization of an n-alkane into micellar solutions formed by mixtures of ionic and nonionic surfactants are discussed in terms of changes in the micellar size with mixture composition. The micellar size changes can be interpreted in terms of the resistance of the Laplace pressure difference across the micelle/solution interface. Values for the average time interval between solubilization events at the oil/water interface have been derived. These show a similar time-scale to the dynamic micellar processes. Effects of the shielding of the ionic component at the micelle/solution interface may be inferred and possible differences in the ability of the surfactant counterion to bind distinguished.

Penetration Enhancer Incorporation in Bilayers

AbstractA preliminary study has been made of the interaction and location of the penetration enhancing agent dodecyl-1-aza-cycloheptane-2-one (Azone) in a system which models certain elements of the lipid arrangements found in the stratum corneum. The model host comprises a nonionic surfactant which forms associated multimolecular structures through hydration interactions with the aqueous component of the system.Azone incorporation into the lamellar bilayer phase leads to a marked increase in ability of the phase to take up water. Small-angle X-ray diffraction and Deuterium NMR measurements indicate the degree of water and azone penetration into the bilayers to be inter-dependent. Similar behaviour is observed for oleyl alcohol but not by hydrotropic materials such as isopropyl alcohol or propylene glycol.The mechanism by which azone promotes the penetration of hydrophilic drugs is indicated to be related to its ability to increase the water capacity of the lipid matrix of the stratum corneum.