Emulsion physical stability

Han, J., and Washington, C. (2005), Partition of antimicrobial additives in an intravenous emulsion and their effect on emulsion physical stability, Int. J. Pharm., 288, 263-271. 

Emulsion Adhesives. The most widely used emulsion-based adhesive is that based upon poly(vinyl acetate)—poly(vinyl alcohol) copolymers formed by free-radical polymerization in an emulsion system. Poly(vinyl alcohol) is typically formed by hydrolysis of the poly(vinyl acetate). The properties of the emulsion are derived from the polymer employed in the polymerization as weU as from the system used to emulsify the polymer in water. The emulsion is stabilized by a combination of a surfactant plus a coUoid protection system. The protective coUoids are similar to those used paint (qv) to stabilize latex. For poly(vinyl acetate), the protective coUoids are isolated from natural gums and ceUulosic resins (carboxymethylceUulose or hydroxyethjdceUulose). The hydroHzed polymer may also be used. The physical properties of the poly(vinyl acetate) polymer can be modified by changing the co-monomer used in the polymerization. Any material which is free-radically active and participates in an emulsion polymerization can be employed. Plasticizers (qv), tackifiers, viscosity modifiers, solvents (added to coalesce the emulsion particles), fillers, humectants, and other materials are often added to the adhesive to meet specifications for the intended appHcation. Because the presence of foam in the bond line could decrease performance of the adhesion joint, agents that control the amount of air entrapped in an adhesive bond must be added. Biocides are also necessary many of the materials that are used to stabilize poly(vinyl acetate) emulsions are natural products. Poly(vinyl acetate) adhesives known as "white glue" or "carpenter s glue" are available under a number of different trade names. AppHcations are found mosdy in the area of adhesion to paper and wood (see Vinyl polymers). 

Driscoll, D. F., Ling, P. R., and Bistrian, B. R. (2007), Physical stability of 20% lipid injectable emulsions via simulated syringe infusion effects of glass versus plastic product packaging, J. Parenteral Enteral Nutr., 31(2), 148-153. 

The concentrated milk is homogenized at 140 to 210 kg/cm2 (2000 to 3000 lb/in2) at about 48°C (Hall and Hedrick 1966). This process is essential to provide adequate physical stability to the milk fat emulsion system to withstand prolonged storage at room temperature (Brunner 1974). However, homogenization lowers the heat stability of concentrated milk products (Parry 1974), which may be due to increased adsorption of casein micelles onto the newly created milk fat globule surfaces, thus making them more sensitive to heat-induced aggregation. 

There are a number of physical-chemical properties of emulsions that are important to consider when developing an emulsion formulation for a drug. These include, but are not limited to, particle (droplet) size, viscosity, osmolarity, and zeta potential, which are used to monitor the physical stability of emulsions. Assays of potency and degradant levels are used to monitor the chemical stability of emulsions. 

Physical stability. As indicated earlier, conventional emulsions are inherently unstable from a physical standpoint. Poor physical stability is ultimately exhibited by phase separation, which can be visually monitored. Certain properties of the emulsion will start to change long before this separation is visually apparent. An increase in particle size is particularly indicative of physical instability, since this monitors the coalescence or Locculation that is part of the process involved in ultimate phase separation. Increases in viscosity (due to Locculation) and changes in zeta potential (arising from a decrease in droplet surface area) are both indicative of poor physical stability. The presence of drug and cosolvents can potentially hasten the phase separation. 

Some ofthe factors that affect the physical stability of emulsions include the type and concentration of surfactant used to stabilize the emulsion, the phase volume ratio (i.e., ratio of oil to aqueous phase), droplet size, compatibility of drug and excipients with the emulsion, and storage condition ofthe emulsion. 

In general, the reduction in the concentration of dispersed phase increases the physical stability of emulsions. Lowerdispersed phase concentration translates to a lower number ofspeciLcsize droplets per unit volume of emulsion. This in turn reduces the degree of droplet interaction, coalescence, and hence phase separation. In general, the dispersed phase concentratid0 col6y volume of total emulsion are acceptable, an<20% desirable. 

Sudden changes in the storage condition of an emulsion is usually detrimental to its physical stability. Whereas slight changes in temperature may be acceptable, large changes in temperature may cause phase inversion, that is, conversion from o/w to w/o and vice versa. The temperature at which this process occurs is called the phase inversion temperature. Usually, emulsions should be stored at least 2C below the phase inversion temperature (Attwood and Florence, 1985). 

Once good physical stability of an emulsion is insured, its commercialization mandates chemical stability of the incorporated drug and other essential components for at least 18 months. Key factors that affect the chemical stability of pharmaceutical emulsions include drug stability in oil, drug stability in aqueous media, drug concentration in oil and emulsion, phase volume ratio, droplet size, presence of excipients, and presence of air and/or peroxide radicals. As mentioned earlier, choice of appropriate antioxidant is important. 

The role of droplet size on drug stability stems from the correlation between droplet size and surface area, and between surface area of droplets and exposure of drug to the aqueous media. If the drug is relatively insensitive to aqueous media, this may not be a major issue however, for the converse situation, development of emulsions with relatively coarser droplet size may offer improved drug stability. Nonetheless, this should be balanced with physical stability of the emulsion as well as the efLciency of drug absorption after oral administration (Toguchi et al., 1990). 

Their use as an injectable warrants assurance of product sterility. Whereas the FDA-preferred heat-sterilization process is acceptable for total parenteral nutritional (TPN) emulsions, it could affect chemical as well as physical stability of emulsions containing therapeutic agents. Recently, data supporting the Liter sterilization of emulsions have been published. 

Extemporaneous addition of drug, alone and/or in solvent, has the tendency to damage emulsion droplets, sometimes resulting in permanent loss of its physical stability. 

Sourdet, S., Relkin, P., Cesar, B. 2003. Effects of milk protein type and pre-heating on physical stability of whipped and frozen emulsions. Colloids Surfaces B. 31, 55-64. 

In most cases, physical instabilities are consequences of previous chemical instabilities. Physical instabilities can arise principally from changes in uniformity of suspensions or emulsions, difficulties related to dissolution of ingredients, and volume changes [6], For instance, some cases where physical stability has been affected are cloudiness, flocculence, film formation, separation of phases, precipitation, crystal formation, droplets of fog forming on the inside of container, and swelling of the container [8],... 

There are an enormous variety of commercial emulsifiers that are employed in emulsion polymerization. Emulsifiers are generally categorized into four major classes anionic, cationic, nonionic and zwitterionic (amphoteric). The anionic and nonionic emulsifiers are the most widely used. In addition, mixtures of emulsifiers are also often used. Since the effects of the molecular structme and chemical and physical properties of an emulsifier on particle formation are still far from being well understood, numerous experimental investigations on particle formation have been carried out to date with various nonionic emulsifiers [99-102], mixed emulsifiers (ionic and nonionic emulsifiers) [18,103-106] and reactive surfactants [33, 107-110]. Recently, polymeric surfactants have become widely used and studied in emulsion polymerizations [111-116]. A general review of polymeric surfactants was published in 1992 by Piirma [117]. Recently, emulsion polymerization stabilized by nonionic and mixed (ionic and nonionic) emulsifiers was reviewed by Capek [118]. 

Solubilization. Surfactants are normally used to physically stabilize emulsion droplets against aggregation by providing a protective membrane around the droplet. Nevertheless, there is often enough free surfactant present in an aqueous phase to form surfactant micelles. These surfactant micelles are capable of solubilizing the nonpolar molecules in their hydrophobic interior, which increases the affinity of nonpolar flavors for the aqueous phase. By a similar argument, reverse micelles in an oil phase are capable of solubilizing polar flavor molecules. 

Gasperlin, M. Tusar, L. Tusar, M. Kristi, J. Smid-Korbar, J. Lipophilic semisolid emulsion systems viscoelastic behaviour and prediction of physical stability by neural 82. network modelling. Int. J. Pharm. 1998,168, 243-254. 

Emulsions have been widely used as vehicles for oral, topical, and parenteral delivery of medications. Although the product attributes of an emulsion dosage form are dependent on the route of administration, a common concern is the physical stability of the system, in particular the coalescence of its dispersed phase and the consequent alteration in its particle-size distribution and phase separation. The stabilization mechanism(s) for an emulsion is mainly dependent on the chemical composition of the surfactant used. Electrostatic stabilization as described by DLVO theory plays an important role in emulsions (0/W) containing ionic surfactants. For 0/W emulsions with low electrolyte content in the aqueous phase, a zeta potential of 30 mV is found to be sufficient to establish an energy maximum (energy barrier) to ensure emulsion stability. For emulsions containing... 

Abd Elbary A, Nour SA, Ibrahim 1. Physical stability and rheological properties of w/o/w emulsions as a function of electrolytes. Pharm Ind 1990 52 357-363. 

Polyoxyethylene alkyl ethers are chemically stable in strongly acidic or alkaline conditions. The presence of strong electrolytes may, however, adversely affect the physical stability of emulsions containing polyoxyethylene alkyl ethers. 

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