Norman D. Weiner

Validation of a flow-through diffusion cell for use in transdermal research

A flow-through finite-dose diffusion cell has been designed for use in transdermal drug delivery research. The diffusion cell consists of an upper donor chamber and a lower receiver compartment through which a continuous supply of fresh solvent flows. The flow is directed to an automatic fraction collector. To validate the flow-through cell, its performance was compared directly against that of a conventional single-reservoir Franz cell. Homologous alkyl p-aminobenzoates were diffused through dimethylpolysiloxane membranes, and permeability coefficients increased with increasing chain length, reaching a plateau at the butyrate ester for both types of cells. This behavior suggests a shift from membrane-controlled diffusion to boundary layer control. Permeation of the butyrate and valerate compounds was significantly faster when the flow-through cell was used, suggesting that better mixing is obtained through the flow-through cell design. Considering the advantages offered in terms of time and labor saved through its use, the flow-through cell with automatic fraction collector appears to be a viable alternative to the conventional Franz cell.

Interfacial properties of hydrocarbons

The interfacial tension of aliphatic hydrocarbon-water systems has been found to increase in a linear fashion as a function of the log of hydrocarbon chain length. Contrary to the literature, values of ϕ and γ H2dO were observed to be also dependent on hydrocarbon chain length. The relationship between hydrocarbon chain length and interfacial tension is actually opposite to that predicted by Antonow’s rule. The results are discussed in terms of hydrocarbon-water interaction and water-structure at the interface.

Application of the Ferguson principle to the antimicrobial activity of quaternary ammonium salts

The activity of three quaternary ammonium salts, dodecyltrimethylammonium chloride, dodecyldimethylethylammonium chloride and dodecylpyridinium chloride, against M. aureus, E. coli and C. albicans has been determined and correlated with the surface properties of these compounds. The Ferguson principle has been applied by using surface concentration to estimate thermodynamic activity. Results obtained for the three quaternary ammonium salts and a particular micro‐organism species were found to be in good agreement with each other when microbiological and surface studies were conducted under identical conditions.

Orientation of monolayers of half-esters of poly(methyl vinyl ether maleic anhydride)

Abstract The effects of subphase pH and certain water-soluble plasticizers on the surface pressure (π)-area (A) isotherms of monolayers of the ethyl and hexyl half-esters of poly (methyl vinyl ether/maleic anhydride) ( PVM MA ) were investigated. An increase in subphase pH (above pH 3.9) causes a decrease in the surface area of the ethyl half-ester monolayer at constant surface pressure but the π-A curve of the monolayer of the hexyl half-ester undergoes little change over a pH range of 3.0 to 6.7. Films of both PVM MA half-esters were found to interact with water-soluble plasticizers. When the plasticizers are compared at the same initial surface pressure, the degree of penetration of monolayers of the ethyl half-ester of PVM MA is practically the same. However, dibutyl phthalate penetrates the hexyl half-ester to a greater extent than does dibutyl adipate or succinate. Based on the results of these experiments, inferences are drawn as to polymer orientation at the air-water interface.

Interaction of gases with monolayers

SIR,-TWO apparently contradictory reports have been made, by Clements & Wilson (1962) and by Evans, Hamilton, Kuenzig & Peltier (1966), about the effects of gaseous anaesthetic agents on monomolecular films. Whereas Clements & Wilson (1962) showed that halothane had a significant effect on the surface pressure of a number of monomolecular films, Evans & others (1966) concluded that halothane did not alter significantly the surface pressure of dipalmitoyl lecithin films. Clements & Wilson, maintained their films at fixed areas and low surface pressures, whilst Evans & others varied their film areas and pressures over a wide range by use of a variable area trough. These latter films were subjected to repeated rapid compression-expansion cycles during which pressures of almost 70 dynes/cm, with average standard deviations of more than 2 dyneslcm, were observed. Based on our experience of the effects of gases on monolayers, the apparent differences in the results are probably directly traceable to basic differences in procedures and techniques. Monomolecular films have been shown to be useful as biological models in the study of membrane interactions with a wide variety of materials in solution (Schulman & Rideal, 1937). It is reasonable to expect that such models could be applied to the study of membrane-gas interactions. In recent work on the effect of gaseous air pollutants on monolayers we have established the need for rigid experimental standardization of the films to be used in gas-film studies. Without such standardization, meaningless and often misleading conclusions could be reached. A precise knowledge of the film properties in the absence as well as in the presence of the gases is required. For example, the rate of film compression, temperature, and history of the film markedly influence the surface pressure-surface area (PA) isotherms of stearic acid monolayers (Rabinovitch, Robertson & Mason, 1960). Whereas the collapse pressure of stearic acid films has been reported to be as high as 62 dynes/ cm using rapid compression methods (Dervichian, 1937), with very slow manual compression rates these films yield collapse pressures of about 15 dynes/cm. At pressures above 15 dynes/cm, the surface pressure values become significantly time dependent. More important, when the rr-A isotherms were obtained for films subjected to repeated compressions and expansions, marked changes occurred in the shapes of the isotherms, especially in condensed regions. Similar effects would be expected for phospholipid films. Furthermore, reproducibility of surface pressure values on successive highly condensed films, can produce serious errors. We have found that an error of 1% in the amount of spreading solution added to the subphase surface can easily produce errors of more than 10 dynes/cni at areas near the limiting area of the film molecules. Such large errors can easily obscure the small effects expected for low concentrations of gases with monolayers. Measurements of surface pressures on a single film, before and after exposure to the gas, would eliminate this source of error. It has been shown that when interactions with the film are relatively weak, the interacting material may be squeezed out of the film at high pressures (Cockbain & Schulman, 1939). It would be expected that in most instances the gas-film interactions would be weak, involving only van der Waals’ forces. Thus a gas which normally interacts with a film under expanded conditions might exhibit little or no interaction with a condensed film or with an expanded film having a history of compression beyond the “equilibrium” collapse pressure. We therefore feel that more meaningful information would be obtained for the interactions of gases with film molecules when these are made on a single

Ideal gaseous behavior of sodium alkyl sulfates at oil-water interfaces

Abstract The existence of an ideal region at the oil-water interface has been demonstrated. A linear relationship between interfacial pressure and low concentrations of sodium decyl sulfate and sodium dodecyl sulfate at water-n-alkane interfaces is reported.

The interaction of nitrogen dioxide with monomolecular films of cholesterol, dihydrocholesterol, and cholesteryl acetate

Abstract The interaction of NO2 with monomolecular films of cholesterol, dihydrocholesterol, and cholesteryl acetate was studied. It appears that two different and relatively independent reactions occur in the presence of NO2. One reaction involves the 3-hydroxy group and leads to products which tend to be desorbed from the surface. The other reaction involves the 5,6 double bond and leads to products which remain on the surface, and which occupy a larger area per molecule than the non-reacted molecule. Thus, the orientation of cholesterol at a gas/ water interface, which is a function of surface pressure, influences both the rate of reaction and the reaction products in the presence of NO2.