AEROSOL Performance Surfactants

AMERICAS CYANAHID CO. AEROSOL Performance Surfactants Diester Sulfosuccinates  

Sodium bistridecyl sulfosuccinate Anionic/70% Liquid in water alcohol Biodegradability Complete Plash Point, F 77 

Surface Tension in Water (minimum) dynes/cm 27 FDA Approvals 21 CFR 178.3400 

High oil solubility with limited water solubility, for emulsion polymerization. Dispersant for pigments, polymers in hydrocarbon and other organic solvents. 

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The adsorption or incorporation of molecules, such as surfactants and polymers, can create a steric repulsion that prevents aggregation [288-290]. This can also increase suspension stability, important for metered-dose inhaler formulations [291]. Lung surfactant coating on the surface of poly(lactic-co-glycolic) acid microparticles has been shown to dramatically improve dry powder aerosol performance by reducing particle-particle interactions [134,292],... 

For the treatment of lung surfactant deficiency in premature human infants suffering from respiratory distress syndrome, limited clinical trials were performed showing that liposomes in the lung-instilled intratracheally either as an aerosolized mist (Ivey et al., 1977) or as a suspension via an endotracheal tube (Fujiwara et al., 1980)—rapidly improved lung function. No adverse effects were observed as a result of the supplementation with surfactant-like material. It appears, therefore, that liposomes are a suitable system for the delivery of major phospholipid components of endogenous lung surfactant. 

Several groups have investigated the effect of surfactants on emitted droplet size. In the early work performed by Polli et al., the surfactant sorbitan trioleate decreased the MM AD of the CFC dexamethasone suspension when added to the formulation (52). A suspension of terbutaline in a CFC system containing sorbitan trioleate surfactant was shown to have little change in emitted particle size when either 2.8 or 14mg/mL of surfactant was added (53). Interestingly, the surfactant had a significant effect on the obscuration (droplet concentration) of the laser diffraction instrument used to determine particle size. Surfactants may lead to an increase in MMAD due to decreased evaporation rates from aerosol droplets. This may occur because of their tendency to associate at the air liquid interface (54). 

Holmes et al. (1998) performed two enzymatic reactions, the lipase-catalyzed hydrolysis of y>-nitrophenol butyrate and lipoxygenase-catalyzed peroxidation of linoleic acid, in w/c microemulsions stabilized by a fluorinated two-chained sulfosuccinate surfactant (di-HCF4). The activity of both enzymes in the w/c microemulsion environment was found to be essentially equivalent to that in a water/heptane microemulsion stabilized by Aerosol OT, a surfactant with the same headgroup as di-HCF4. The buffer 2-(A-morpholino)ethanesulfonic acid (MES) was used to fix the pH in the range 5-6. 

The use of surfactants to modify the surface tension of an aerosol and alter its droplet size distribution has shown that their influence depends strongly on the characteristics of the solution to be aerosoled. The span, defined as 90% undersize —10% undersize/50% undersize, gives a measure of the width of the volume distribution relative to the median diameter of the droplets formed in the aerosoling process. Comparative studies performed with commercial air-jet and US nebulizers have shown that, under similar working conditions, the latter provide less heterodispersed aerosols, with span values ranging from 1.50 to 1.75, which are similar for aqueous drug solutions in the presence and absence of surfactants [156]. 

Table II lists the surfactants which exhibited the highest degree of solubility in pentane. Saturated solutions of these surfactants in CO2 and 23 C and 1000 -2500 psia were tested in the high pressure viscometer, with and without water present. However, none of these saturated solutions or a solution of CO2 and Aerosol OT, which is known to form reverse micelles in supercritical light alkane systems, (15) resulted in viscosity increases relative to pure CO2. It must be noted that experimental verification of reverse micelle formation was not performed. This method of increasing the CO2 viscosity was not pursued because we felt that (1) the low viscosity of the continuous phase, CO2, would not promote the formation of viscous, micellar solutions, and (2) the surfactants listed in Table II were the most likely to satisfy our requirements. Their inability to increase the viscosity of 002 whether micelles formed or not, did not lead us to believe other surfactants would yield dramatically better results.

All types of micro emulsions were obtained in salinity scans with mixtures of Aerosol MA (sodium dihexyl sulphosuccinate) and twin-tailed (Guerbet and Exxon type) alcohol ethoxy and propoxy sulphates for perchloroethylene (PCE), carbon tetrachloride, 1,2-dichlorobenzene and trichloroethylene [59] at 25°C. At lower temperatures, however, stable macro emulsions are formed. Chloroform, 1,2-dichloroethane and other chlorinated hydrocarbons were found to be too polar for those anionic surfactants. Extremely hydrophilic and temperature-insensitive surfactants are necessary for effective solubilisation of chlorinated hydrocarbons yielding Winsor III systems. N-methyl-N-D-glucalkaneamide surfactants showed good performance for DNAPL solubilisation even at 16°C [56]. 

Supersolubilisation of NAPL can be achieved by adding lipophilic linkers to the system. Best results for chlorinated hydrocarbons were obtained with both hydrophilic and lipophilic linkers [71]. Lipophilic linkers increase the interaction between surfactant and oil [72], and hydrophilic linkers the interaction between surfactant and water. Systems with Aerosol MA as surfactant, sodium mono- and dimethyl naphthalate as hydrophilic linker, and dodecanol as lipophilic linker display the best performance regarding efficiency, economy and environmental aspects [65]. 

Processes for adenovirus purification typically end with concentration, formulation, and sterile filtration operations [40, 80,106]. Concentration and formulation are usually carried out in ultra-filtration units equipped with 100-300-kDA membranes [40,106]. The exact composition of the formulation buffer will depend on the intended application, mode of administration (injectable, aerosol), and required short-term and shelf stability [104,123]. A typical liquid formulation may include an aqueous buffer supplemented with cryoprotectants (e.g., sucrose) and stabilizers such as the nonionic-surfactant polysorbate-80, the chelating agent EDTA, and the oxidation inhibitors ethanol and histidine [123]. Filtration under sterile conditions is typically performed with 0.22-pm membranes [103,106]. 

In a series of papers (24-29) Eicke and co-workers reported results of thorough studies performed on inverse micellar systems involving hydrocarbons such as benzene or isooctane and surfactants such as AY or AOT aerosols. Dielectric, conductance, ultracentrifugation, NMR, light scattering, fluorescence depolarization and photon correlation spectroscopy techniques were used. The main conclusions arrived at are the following ones, as expressed in C29). For water-to-AOT molar ratios smaller than 10, water-in-isooctane systems consist of dispersions of hydrated soap aggre-... 

Fontaine and co-workers (206), on the basis of these similarities, envisaged that high levels of drag reduction can be achieved by combining low concentrations of pol5mier and surfactants with microbubble injection at low injection rates. The influence of homogeneous surfactant (Aerosol OT) and homogeneous polymer (PEO) solutions on the performance of microbubble skin friction reduction... 

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