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Choice of emulsifying agent 1 Toxicity and irritancy considerations 2 The choice of emulgent to be used will depend not only on its emulsifying ability, but also on its route of administration and, consequently, on its toxicity. It will be noted that most of these emulsifying agents are non-ionic, having a tendency to be less irritant and less toxic than their anionic, and particularly their cationic counterparts. The concentrations of ionic emulsifying agents necessary for emulsification will be irritant to the gastrointestinal tract and have a laxative effect, and should not be used for oral emulsions. 3 Cationic surfactants in general are toxic even at lower concentrations. The emulgent cetrimide is limited to externally used preparations, where its antiseptic properties are of use. Some emulgents, such as the anionic alkali soaps, often have a high pH and are thus unsuitable for application to broken skin. Even on normal intact skin with a pH of 5.5, the application of such alkaline materials can cause irritation. Some emulsifiers, in particular, wool fat can cause sensitization reactions in susceptible people. When choosing an emulgent for parenteral use it must be realized that only certain types of non-ionic material are suitable. These include lecithin, polysorbate 80, methylcellulose, gelatin and serum albumin. The hydrophile–lipophile balance (HLB) concept 4 Each surfactant is allocated an HLB number usually on a scale of 0–20, based on the relative proportions of the hydrophilic and hydrophobic part of a molecule. Water-in-oil emulsions are formed generally from oil-soluble surfactants of low HLB number and oil-in-water emulsions from more hydrophilic surfactants of high HLB number. 5 The method of selection is based on the observation that each type of oil will require an emulsifying agent of a specific HLB number to produce a stable emulsion. Thus, oils are often designated two “required” HLB numbers, one low and one high, for their emulsification to form water-in-oil and oil-in-water emulsions respectively. A series of emulsifiers and their blends with HLB values close to the required HLB of the oil are then examined to see which one forms the most stable emulsion. "Required HLB" Values of some Ingredients 6 "Required HLB" for w/o o/w Ingredient Emulsion Acid, Stearic 6 15 Alcohol, Cetyl __ 15 Alcohol, Stearyl __ 14 Lanolin, Anhydrous 8 10 Fat, Wool 8 10 Oil, Cottonseed 5 10 Oil, Mineral 5 12 Petrolatum 5 12 Paraffin, Liquid 4 12 Wax, Beeswax 4 12 HLB Values of some Surfactants 7 Surfactant HLB Sorbitan trioleate (Span 85) 1.8 Sorbitan tristearate (Span 65) 2.1 Sorbitan sesquioleate (Arlacel 83) 3.7 Glyceryl monostearate, NF 3.8 Oleic acid 4.3 Sorbitan monooleate, NF, (Span 80) 4.3 Sorbitan monostearate, NF, (Span 60) 4.7 Sorbitan monopalmitate, NF, (Span 40) 6.7 Sorbitan monolaurate, NF, (Span 20) 8.6 HLB Values of some Surfactants 8 Surfactant HLB Polyoxyethylene sorbitan tristearate, (Tween 65) 10.5 Polyoxyethylene sorbitan trioleate, (Tween 85) 11.0 Polyethylene glycol 400 monostearate 11.6 Polysorbate 60, NF, (polyoxyethylene sorbitan monostearate) (Tween 60) 14.9 Polyoxyethylene monostearate (Myrj 49) 15.0 Polysorbate 80, NF, (polyoxyethylene sorbitan mono-oleate) (Tween 80) 15.0 Polysorbate 40, NF, (Tween 40) 15.6 Polysorbate 20, NF, (polyoxyethylene sorbitan mono-laurate) (Tween 20) 16.7 Potassium oleate 20.0 Sodium lauryl (dodecyl) sulphate 40.0 An example of an o/w emulsion: 9 Liquid paraffin 35% Wool fat 1% Cetyl alcohol 1% Emulsifier system 5% Water to 100% The total percentage of oil phase is 37 (35%+1%+1%) and the proportion of each is: Liquid paraffin 35/37 * 100 = 94.6% Wool fat 1/37 * 100 = 2.7% Cetyl alcohol 1/37 * 100 = 2.7% The total required HLB num12/12/2011ber is 10 obtained as follows: Liquid paraffin (HLB 12) 94.6/100 * 12 = 11.4 (nearest decimal digit) Wool fat (HLB 10) 2.7/100 * 10 = 0.3 (nearest decimal digit) Cetyl alcohol (HLB 15) 2.7/100 * 15 = 0.4 (nearest decimal digit) Total required HLB = 12.1 11 From theoretical considerations, this particular formulation requires an emulgent blend of HLB 12.1 in order to produce the most stable emulsion. It must be realized, however, that the presence of other ingredients, particularly those that may partition into the oil phase, can also affect the required HLB value. It is therefore often necessary to prepare a series of emulsions using blends of a given pair of non-ionic emulsifying agents covering a wide range of HLB values. This is also important if the required HLB for an oil phase is not available. The HLB value of the emulgent blend giving the most stable emulsion is the required value for that oil phase. 12 Assuming that a blend of sorbitan mono-oleate (HLB 4.3) and polyoxyethylene sorbitan mono-oleate (HLB 15) is to be used as the emulsifying system, the proportions of each to be added to the emulsion to provide an HLB of 12.1 are calculated as follows. Let A be the percentage concentration of the hydrophilic and B the percentage of the hydrophobic surfactants required to give a blend having an HLB value of x. Then: 13 A= and B = 100 - A 14 In our example, therefore: A= = 72.9 B = 100 – 72.9 = 27.1 15 Because the total percentage of emulgent blend in the formulation is 5, the percentage of each emulsifier will be: Sorbitan monooleate 5 * (27.1/100) = 1.36 polyoxyethylene sorbitan mono-oleate 5 – 1.36 = 3.64 Notes on the previous example 16 Although the HLB concept narrows the range of emulsifiers to select and provides a schematic approach for the formulator, it is limited by its strict relation to molecular structure of the individual surfactants. The concept does not consider the total emulsion and is therefore insensitive to between emulsifier components, the influence of changes, or the in the emulsion. Consequently, not all emulsifier blends of the correct HLB form stable systems. Activity and HLB value of emulsifiers 17 Activity Assigned HLB Antifoaming 1–3 Emulsifiers (w/o) 3–6 Wetting agents 7–9 Emulsifiers (o/w) 8–18 Solubilizers 15–20 Detergents 13–15 Phase Inversion Temperature (PIT) 18 The use of the HLB system has several disadvantages, including the inability to take into account the effects of temperature, the presence of additives and the concentration of the emulsifier. It is possible to overcome some of these problems. An o/w emulsion stabilized by non-ionic emulgents will, on heating, invert to form a w/o product. This is because, as the temperature increases, the HLB value of a non- ionic surfactant will decrease as it becomes more hydrophobic. At the temperature at which the emulgent has equal hydrophilic and hydrophobic tendencies (the phase inversion temperature) the emulsion will invert.
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