General formulation of Emulsions and MCQs for GPAT, NIPER, Pharmacist and Drug Inspector exam

FORMULATION COMPONENTS:

Oil Phase – Various chemical types of oils are used in the preparation of pharmaceutical emulsions, including hydrocarbons, simple esters, fatty acids, fixed and volatile oils, and waxes. The selection of oil phase is based on the solubility of the drug in the oil phase, oil/water partition coefficient of the drug, its tactile characteristics and feel, if the emulsion is meant for topical application. The most widely used oils in oral preparations are cod liver oils or various fixed oils of vegetable origin(e.g. cottonseed, arachis and maize oils) as nutritional supplements and non biodegradable mineral and castor oils that provide a local laxative effect. For topically applied emulsions, hydrocarbons such as hard and soft paraffin are widely used both as the vehicle for the drug and for their occlusive and sensory characteristics. Glycols are used to formulate non aqueous emulsions. The choice of oil is severely limited in parenteral emulsions. Purified soybean, sunflower, sesame and cottonseed oils composed mainly of long-chain triglycerides have been used for many years as they are resistant to rancidity and have few clinical side effects.

Table 1 –  Ingredients for oil phase of emulsions

Emulsifiers – Emulsifiers are used both to promote emulsification at the time of manufacture and to control stability during a shelf life that can vary from days to months or years. For convenience, most  pharmacy texts classify emulsifiers into three groups: (1) surface-active agents, (2) hydrophilic colloids (macromolecules) and (3) finely divided solids. The surfactants are primarily used as emulsifiers, whereas hydrophilic colloids and finely divided solids find their greatest utility in the form of auxiliary emulsifiers. The choice of emulsifier (surfactants) is determined by the type of emulsion desired, the required shelf life stability, the surfactant cost, the clinical use and the toxicity. For example, the addition of anionic surfactant is restricted to formulations meant for external use.

• The appropriate emulsifier or emulsifier mixture can be chosen by preparing a series of emulsions with a range of surfactants of varying HLBs.
• Mixtures of surfactants with high HLB and low HLB give more stable emulsions than do single surfactants.
• The solubility of surfactant components in both the disperse phase and the continuous phase maintains the stability of the surfactant film at the interface.
• The formation of a viscous network of surfactants in the continuous phase prevents their collision, and this effect overrides the influence of the interfacial layer and barrier forces due to the presence of adsorbed layers.

Four categories of surface-active agents are used to stabilize pharmaceutical emulsion/cream formulations: (1) anionic, (2) cationic, (3) nonionic and (4) amphoteric.

Determination of emulsifier amount – The least amount of surfactant mixture required for optimal stability of an emulsion is determined by the amount of water that can be solubilized in a given oil-plus-surfactant(s) mixture under carefully controlled temperature and stirring conditions. For this purpose, 10 g of the oil–surfactant mixture is weighed in a glass vial. Water is added in 0.1 mL increments. The mixture is shaken and allowed to stand at the equilibration temperature (temperature at which this system is fluid) until all air bubbles have escaped. The addition of water (0.1 mL increments) is continued until the system remains permanently turbid. If the initial oil–surfactant mixture is not clear, it will usually become clear upon the addition of water and then will become cloudy again upon continued addition of water. This second cloudpoint is the end of titration. As a rule, the most stable o/w emulsion with the finest particle size results at that oil–surfactant ratio that can tolerate the largest quantity of water and still remain clear.

Auxiliary Emulsifiers –

Hydrophilic colloids: Polymers that are water sensitive (swellable or soluble) have some utility as primary emulsifiers; however, their major use is as an auxiliary emulsifier and as a thickening agent. Clays such as bentonite swell in the presence of water and are used for building the viscosity of emulsions. Other clays such as attapulgite thicken primarily because of particle anisotropy.

Table 2 –  Hydrophilic colloids useful in emulsion technology

Finely divided solids – Finely divided solids have been shown to be good emulsifiers, especially in combination with surfactants and/or macromolecules that increase viscosity. This includes polar inorganic solids, such as heavy metal hydroxides, certain nonswelling clays and pigments. Even nonpolar solids (e.g. carbon or glyceryltristearate) can be used. Polar solids tend to be wetted by water to a greater extent than by the oil phase, whereas the reverse is true for nonpolar solids. In the absence of surfactants, w/o-type emulsions are favoured by the presence of nonpolar solids, presumably because the wetting by oil facilitates the coalescence of oil droplets during the initial steps of emulsification. An analogous interpretation may be given for the tendency of polar solids to favour water as the external phase.

Viscosity Modifiers – Once the desired emulsion and emulsifiers have been chosen, a consistency that provides the desired stability and yet has the appropriate flow characteristics must be attained. It is well known that the creaming of fluid emulsions depends on the surface characteristics of the interfacial film as well as on the rheological character. The creaming rate of suspended  globules is inversely proportional to the viscosity in accordance with Stokes’ law. When all other variables are held constant, an increase in viscosity generally minimizes creaming, rising or sedimentation. In the case of o/w emulsions, gums and clays are added to increase viscosity, whereas for w/o emulsions, polyvalent metal soaps or high melting waxes and resins are used.

Preservatives – Emulsions often contain a number of ingredients, such as proteins, carbohydrates, phosphatides and sterols, all of which readily support the growth of various microbes. Even in the absence of any of the aforementioned natural ingredients, the intimate contact of an oil and water allows microbes to establish themselves. As a result, the inclusion of a preservative is a necessary part of the formulation process. The preservative must first meet the general criteria of low toxicity, chemical compatibility, stability to heat and storage, acceptable taste, odour and colour, and reasonable cost. Since microorganisms can reside in water, in the oil phase or in both, it is customary that the preservative should be available at an effective level in both phases. The esters of p-hydroxybenzoic acid are particularly good examples because methyl ester (methyl paraben) is water soluble, whereas propyl ester (propyl paraben) is oil soluble.

Antioxidant – Oils are subjected to autoxidation upon exposure to air. Upon autoxidation, unsaturated oils, such as vegetable oils, give rise to rancidity, resulting in unpleasant odour, appearance and taste. Autoxidation is a free radical chain oxidation reaction. It can be inhibited, therefore, by the absence of oxygen, by a free radical chain breaker or by a reducing agent. The choice of a particular antioxidant depends on its safety, acceptability for a particular use and its efficacy. Antioxidants are commonly used at concentrations ranging from 0.001 to 0.1%. Butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), L-tocopherol and alkyl gallates are particularly popular in pharmaceuticals and cosmetics. BHT and BHA have a pronounced odour and should be used at low concentrations. Alkyl gallates have a bitter taste, whereas L-tocopherol is well suited for oral emulsions.

Multiple Choice Questions:

1.Which of the following components are used in formulation of emulsions?

a)Oil Phase

b)Viscosity Modifiers

c)Finely divided solids

d)All of these

2.Various chemical types of oils are used in the preparation of pharmaceutical emulsions, including

a)hydrocarbons

b)simple esters

c)fatty acids

d)all of these

3.The selection of oil phase is based on the solubility of the drug in the oil phase, oil/water partition coefficient of the drug.

a)true

b)false

4.The most widely used oils in oral preparations are

a)cottonseed

b)arachis

c)maize oils

d)all of these
5.For topically applied emulsions which of the following oil phase is/are used?

a)hard paraffin

b)soft paraffin

c)both of these

d)none of these

6.Which of the following oils are resistant to rancidity?

a)soybean oil

b)sunflower oil

c)sesame oil

d)all of these

7.Which of the following is not an ester oil?

a)Vegetable oils

b)Animal fats

c)Lanolin

d)Polyoxypropylenes

8.Which of the following is plant wax?

a) Candelilla

b)Bees

c) i-propylmyristate

d)All of these

9.The surfactants are primarily used as emulsifiers, whereas hydrophilic colloids and finely divided solids find their greatest utility in the form of auxiliary emulsifiers.

a)true

b)false

10.The choice of emulsifier (surfactants) is determined by

a)the type of emulsion desired

b)the required shelf life stability

c)the surfactant cost

d)all of these

11.The least amount of surfactant mixture required for optimal stability of an emulsion is determined by the amount of water that can be solubilized in a given oil-plus-surfactant(s) mixture under carefully controlled temperature and stirring conditions.

a)true

b)false

12.Auxiliary Emulsifiers are

a)Hydrophilic colloids

b)Hydrophobic colloids

c)Both of these

d)None of these

13.Gum karaya is

a)Polysaccharide

b)Protein

c)Cellulose

d)Synthetic

14.Gelatin is

a)Polysaccharide

b)Protein

c)Cellulose

d)Synthetic

15._______is well suited for oral emulsions.

a)Alkyl gallates

b)L-tocopherol

c)BHA

d)All of these

Solutions:

1. d)All of these
2. d)all of these
3. a)true
4. d)all of these
5. c)both of these
6. d)all of these
7. d)Polyoxypropylenes
8. a) Candelilla
9. a)true
10. d)all of these
11. a)true
12. a)Hydrophilic colloids
13. a)Polysaccharide
14. b)Protein
15. b)L-tocopherol

References:

1. Gaurav K. Jain Theory and Practice of Physical Pharmacy, 1st edition 2012 Elsevier, page no. 229-233.
2. Remington Essential of Pharmaceutics, 1st edition 2013, page no. 450, 451.
3. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery systems, 10th edition, page no. 468-470.

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