Emulsions preservative distribution

In a multiphase formulation, such as an oil-in-water emulsion, preservative molecules will distribute themselves in an unstable equilibrium between the bulk aqueous phase and (i) the oil phase by partition, (ii) the surfactant micelles by solubilization, (iii) polymeric suspending agents and other solutes by competitive displacement of water of solvation, (iv) particulate and container surfaces by adsorption and, (v) any microorganisms present. Generally, the overall preservative efficiency can be related to the small proportion of preservative molecules remaining unbound in the bulk aqueous phase, although as this becomes depleted some slow re-equilibration between the components can be anticipated. The loss of neutral molecules into oil and micellar phases may be favoured over ionized species, although considerable variation in distribution is found between different systems. 

In a multiphase formulation, such as an oil-in-water emulsion, preservative molecules will distribute themselves in an unstable equilibrium between the bulk aqueous phase and (i) the oil phase by partition, (ii) the surfactant micelles by solubilization,... 

V. Mishra, S. M. Kresta, J. H. Masliyah 1998, (Self-preservation of the drop size distribution function and variation in the stability ratio for rapid coalescence of a polydisperse emulsion in a simple shear field), J. Colloid Interface Sci. 197, 57. 

Benzoic Add, USP. Benzoic acid and its esters occur naturally in gum benzoin and in Peru and tolu balsam.s. It is found as a white crystalline solid that slowly sublimes at room temperature and is steam distillable. It is slightly soluble in water (0.3%) but more. soluble in alcohol and in other polar organic. solvents. It has a pK of 4.2. Benzoic acid is used externally as an antiseptic in lotions, ointment.s. and mouthwashes. It is mure effective as a preservative in foods and pharmaceutical products at low pH (Ic.ss than the pK ). When used as a preservative in emulsions, its effectiveness depends on both pH and distribution into the two pha.scs. ... 

Since preservative efficacy may vary according to the product, analysis of preservative content often has to be supported by a preservative challenge test. This may also be relevant with certain emulsion systems where the preservative may partition between the different oil and water phases. For simple distribution phenomena, the partition or distribution law normally applies. 

As for polymerization of hydrophobic monomers in the bicontinuous phase of microemulsions, the initial structure is not preserved upon polymerization. However, a notable difference from the former systems is that the final system is a microlatex that is remarkably transparent (100% optical transmission), fluid, and stable, with a particle size remaining unchanged over years even at high volume fractions ( 60%) [20]. The microlatex consists of water-swollen spherical polymer particles with a narrow size distribution according to QELS and TEM experiments. This result is of major importance with regard to inverse emulsion polymerization, which is known to produce unstable latices with a broad particle size distribution [23]. 

Safety and hygiene effects. Limitations related to process/product safety can in some cases be solved by the use of microstructured reactors. For example, very exothermic reactions and explosive gas mbctures have been demonstrated to operate safely in structured reactors [12]. The transport of hazardous chemicals could also find sustainable solutions in the development of distributed production in miniaturized plants [13]. In the frame of product engineering, micromixers allowed the quantity of emulsifiers and preservatives required to stabilize emulsions for pharmaceutical applications to be reduced [14]. 

Sorbic acid has a more suitable fat-water distribution than methylparaben, which makes it better applicable in emulsions. For solubilisates there is however a problem to overcome because sorbic acid adsorbs onto polysorbate, which is often used as a solubilising agent. Therefore the processed quantity of sorbic acid should be larger than the solubility of sorbic acid in water. Potassium sorbate is used to achieve this. Potassium sorbate is dissolved in water and then converted to sorbic acid using citric acid. Part of the sorbic acid dissolves in the lipid phase and adsorbs to the polysorbate. The free sorbic acid serves to preserve the aqueous phase [33]. See further Sect. 23.8.6. 

Micro-organisms replicate only in the presence of water. The activity of preservatives depends therefore on the concentration of the free and active form in the aqueous phase of the preparation. Free refers to the binding that some preservatives can have with active substances, excipients or packaging materials. Examples of the binding of preservatives are the adsorption of phenylmercuric compounds to rubber stoppers, the adsorption of benzalkonium chloride to silicon rubber tubes and to cellulose nitrate-membrane filters, the solubilisation of methyl parahydroxybenzoate by polysorbate 80 [49] and by sodium lauiyl sulfate [50] and the migration (distribution) towards the lipid phase of methyl parahydroxybenzoate in emulsions. 

The chemical stability of the biocide and the accuracy of dosing of it into the emulsion can be determined in a number of ways, e.g. by high performance liquid chromatography (HPLQ. This can be used as a quality control test method, carried out to confirm if the emulsion is adequately preserved and has a standard specification, along with other specifications of solids content, pH, viscosity, particle size distribution, residual monomer concentration, etc. 

Partition coefficient. Lipophilic preservatives tend to accumulate in the lipid phase of a formulation. This phenomenon is particularly important when planing preservative systems for emulsions, where the partition coefficient, as the ratio of preservative concentrations in the oil and water phases respectively, is a significant index of how they partition in emulsions. Adding alcohol to an aqueous milieu can shift the distribution coefficient in favour of the aqueous phase. In contrast, non-ionic surfactants tend to shift the partition coefficient in favour of the oil phase, resulting in a reduction of preservative efficacy in the water phase (WallhauBer, 1984). 

Due to its favourable distribution coefficient sorbic acid is the preferred preservative for fat containing food, like margarine or other fat-emulsions like mayonnaise or dressings. In the latter case potassium sorbate is often combined with sodium benzoate. 

The use of emulsions in medicine demands a knowledge of the distribution of added agents to the formulation. Flavouring agents, preservatives, stabilizers and, of course, therapeutically active substances are added to emulsion formulations and are distributed at equilibrium between the continuous phase and the disperse... 

For the tertiary droplets and related prill powder particle size of SE and DE small size and a narrow size distribution are desirable for most of the industrial apphca-tions. As discussed in the previous sections, the criteria for keeping the microstructure of an emulsion unchanged, is equally important for applications where functional components shall be preserved within such microstructure. To obtain the small spray droplet and still keeping the emulsion microstmcture unchanged is technologically enormously challenging. 

Experiments have been conducted on emulsions containing 20% v/v of a mixture of heptane (90% v/v) and hexadecane (10% v/v), emulsified with 0.35% nonionic surfactant in the aqueous phase. The aqueous phase also contained 0.2% sodium azide as preservative. The emulsions were prepared using a Waring Blender, and their droplet size distribution revealed a polydisperse distribution, with weight mean radius 2 im. The emulsion was stable to coalescence during the timescale of the experiments. 

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