Flocculation emulsion formulation

Coalescence and flocculation are strongly related to one another. Reducing the rate of drop coalescence is one of the main purposes of surfactants in emulsion formulations. The reduction in the interfacial tension on addition of surfactant itself increases the stability of the emulsion with respect to its component phases. However, the role of surfactants is much greater than this and they act to reduce droplet coalescence in several additional ways. 

Content uniformity and long-term stability of a pharmaceutical product are required for a consistent and accurate dosing. Aggregation of dispersed particles and resulting instabilities such as flocculation, sedimentation (in suspensions), or creaming and coalescence (in emulsions) often represent major problems in formulating pharmaceutical disperse systems. 

Example. Cream liqueurs are an example of a food emulsion for which good stability over a period of several years is required. Thus the processes of creaming, flocculation, and coalescence must all be controlled in the formulation. The product must have a cream-like appearance and a relatively high alcohol content. A possible composition might be ... 

The chapter should allow an appreciation of the factors leading to emulsion stability and physical instability, including flocculation and coalescence. Approaches to the formulation of emulsions to provide vehicles for drug delivery and parenteral nutrition (the main uses in pharmacy) should be understood. 

I 70 Formulation of Liquid/Uquid Dispersions (Emulsions) Table 10.4 Half-life of emulsion flocculation. 

Equation (12.10) also shows that when > 0.5 - that is, when the solvency of the medium for the chains becomes poor - Gj j will be negative and the interaction will become attractive. Thus, it is important to ensure that the solvent used to prepare the W/O emulsion is a good solvent for the PHS chains, otherwise flocculation of the water droplets (perhaps followed by their coalescence) may occur. Fortunately, the PHS chains are soluble in most hydrocarbon solvents used in most formulations. The condition = 0.5 is referred to as 0-solvent, and this denotes the onset of a change from repulsion to attraction. Thus, to ensure steric stabilisation by the above mechanism it must be ensured that the chains are kept in better than 0-solvent. 

All parenteral emulsions are oil-in-water formulations, with the oil as the internal phase dispersed as fine droplets in an aqueous continuous phase. An emulsifier, usually egg or soy lecithin, is needed to lower the interfacial tension and prevent flocculation and coalescence of the dispersed oil phase. Mechanical energy, usually in the form of homogenization, is required to disperse the oil phase into droplets of a suitable size. For IV administration, the droplet size should be below 1 p.m to avoid the potential for emboli formation. 

Photochemical stability of suspensions and emulsions is a rather complicated area. The optical properties of a disperse system (transmission of photons through the formulation and spread of optical irradiation) will depend on the size of the particles or droplets in the disperse phase, the fractional relationship between the disperse and homogenous phases, flocculation in the system, and physicochemical properties of the disperse and homogenous phases. The photochemical stability of a drug formulated as an emulsion will partly depend on the photochemical reactivity of the drug in the lipophilic and hydrophilic phases. The distribution of the drug between the two immiscible phases is an essential aspect to consider as part of an evaluation. Influence of the solvent properties on photochemical reactivity is covered in Section 14.2.2. 

The polymer emulsions can be concentrated by headng imder vacuum to remove excess water and organic solvent by evaporation [43]. In this method, it is possible to reduce the water down to 2% and to increase the polymer crmtent in the emulsion up to 70% [30]. To be effective flocculants, the polymer emulsions must exhibit excellent freeze-thaw properties [11]. Another important requirement concerns their ability to invert wiA excess water to yield a highly viscous dilute polymer solution used as such for applications. A wetting ageru like a surfactant with a high HLB value (10-14) may be used to facilitate inversion. Typical surfactants are oxyethylated alkylphenols, fatty alcohols or fatty acids. They are added (up to 5% by weight of the total formulation) to water or to polymer emulsion prior to dissolution [22,43]. 

Typical excipients used in parenteral suspensions include surfactants that are used to stabilise emulsions and suspensions as wetting agents (polysorbate 80, poloxamer), as micelle makers for the preparation of solubilisations and to influence the flocculation and deflocculation behaviour of a dispersed system (carmellose sodium, polyvidone). Paren-terally used surfactants in high concentrations are toxic and may cause venous irritation and occasional thrombophlebitis. However, these high concentrations are not necessary to formulate stable parenteral suspensions. 

As an alternative to pressed powders, liquid foundations have attracted special attention in recent years. Most foundation make-ups are made of O/W or W/0 emulsions in which the pigments are dispersed either in the aqueous or the oil phase. These are complex systems consisting of a suspension/emulsion (suspoe-mulsion) formulation. Special attention should be paid to the stability of the emulsion (absence of flocculation or coalescence) and suspension (absence of flocculation). This is achieved by using specialised surfactant systems such silicone polyols or block copolymers of poly(ethylene oxide) and poly(propylene oxide). Some thickeners may be also added to control the consistency (rheology) of the formulation. 

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