Emulsions: Manufacturing procedure and Question Answer for GPAT, NIPER, Pharmacist and Drug Inspector exam
EMULSIFICATION TECHNIQUES (EMULSION FORMATION):
1.Conventional method
– Dry gum method
– Wet gum method
2.Condensation method
3.Phase inversion technique
4.Low-energy emulsification
5.Spontaneous emulsification
Emulsion preparation by the commonly used dispersion method requires a sequence of processes for breaking up the internal phase into droplets and for stabilizing them in the external phase. Usually, the breakup of the internal phase (by physical means) is fairly rapid; however, it is believed that the stabilization step and the rate of coalescence are time and temperature dependent. The application of energy in the form of heat, mechanical agitation, ultrasonic vibration or electricity is required to reduce the internal phase into small droplets. Almost all methods used for breaking up the internal phase into droplets depend on ‘brute force’ and require some sort of agitation. After the initial breakup into droplets, they continue to be subjected to additional forces due to turbulence, which deform the droplet and further breaks them down into smaller droplets. Various types of equipment are available to affect droplet breakup and emulsification either in the laboratory or in production. Irrespective of size and minor variations, such equipment can be divided into four broad categories:
(1) mechanical stirrers, (2) homogenizers, (3) ultrasonifiers and (4) colloid mills.
1.Conventional method – Conventionally, mixing of immiscible liquids on a small scale is carried out. Emulsions thus obtained are coarse and require further homogenization.
Dry Gum Method: Emulsifier is triturated with the oil in perfectly dry porcelain mortar then water is added at once. Triturate immediately, rapidly and continuously (until get a clicking sound and thick white cream is formed, this is primary emulsion) the remaining quantity of water is slowly added to form the final emulsion.
Wet Gum Method: Triturate gum with water in a mortar to form a mucilage oil is added slowly in portions the mixture is triturated. After adding all of the oil, thoroughly mixed for several minute to form the primary emulsion. Once the primary emulsion has been formed remaining quantity of water is added to make the final emulsion.
2.Condensation method – Vaporization is an effective way of breaking almost all the bonds between the molecules of a liquid. It is possible, therefore, to prepare emulsions by passing the vapour of a liquid into an external phase that contains suitable emulsifying agents. This process of emulsification, called the condensation method, is relatively slow, is limited to the preparation of dilute emulsions of materials having a relatively low vapour pressure and is therefore primarily of theoretical importance.
3.Phase inversion technique – The most important influence that temperature has on an emulsion is probably inversion. Consider an o/w emulsion stabilized by a nonionic surfactant. Such o/w emulsion contains oil-swollen micelles of the surfactant as well as emulsified oil. When the temperature is raised, the water solubility of the surfactant decreases; consequently, the micelles are broken, and the size of emulsified oil droplets begins to increase. A continued rise in the temperature causes separation into an oil phase, a surfactant phase and water. It is near this temperature that the now water-insoluble surfactant begins to form a w/o emulsion containing both waterswollen micelles and emulsified water droplets in a continuous oil phase. The temperature at which the inversion occurs depends on emulsifier concentration and is called phase inversion temperature (PIT). This type of inversion can occur during the formation of emulsions, since they are generally prepared at relatively high temperatures and are then allowed to cool down to room temperature. Emulsions formed by a phase inversion technique are generally considered quite stable and are believed to contain a finely dispersed internal phase. The PIT is generally considered to be the temperature at which the hydrophilic and the lipophilic properties of the emulsifier are in balance and is therefore also called the HLB temperature.
4.Low-energy emulsification – In low-energy emulsification, all of the internal phase, but only a portion of the external phase, is heated. After emulsification of the heated portions, the remainder of the external phase is added to the emulsion concentrate. In those emulsions in which a PIT exists, the emulsion concentrate is preferably prepared above the PIT, which results in emulsions having extremely small droplet size. By careful control of the variables (such as emulsification temperature, mixing intensity and the amount of external phase), it is reportedly possible to produce emulsions with smaller and more uniform particle size than those resulting from the conventional process.
5.Spontaneous emulsification – Spontaneous emulsification occurs when an emulsion is formed without the application of any external agitation. Emulsifiable concentrates and microemulsions are typical examples. Microemulsions commonly form spontaneously, but not all spontaneous emulsions are transparent. The phenomenon of spontaneous emulsification can be observed when a drop of oil is placed on an aqueous solution of an emulsifier, in which case the interface becomes extremely unstable and results in the formation of fine droplets. Spontaneous emulsification evidently is not practiced commercially. In general, the considerations applicable to opaque emulsions are also pertinent to the preparation of clear emulsions. The amount of internal phase in clear emulsions or in solubilized systems is generally lower than that in opaque emulsions. Most emulsion technologists have found that an increase in the surfactant concentration(s) reduces the opacity of all types of emulsions and further increase can result in solubilization.
PRODUCTION ASPECTS: In routine production, it is customary to prepare emulsions by a batch process using kettles, agitators and related equipment. However, it is possible to design combinations of equipment that permit continuous manufacturing of emulsions. The selection of commercial equipment for the production of emulsions is based in part on the production capacity and the power requirements for various types of apparatus.
In the laboratory development of emulsions, it is common practice to prepare an oil phase containing all the oil-soluble ingredients and to heat it at about 5–10°C above the melting point of the highest melting ingredient. The aqueous phase is normally heated to the same temperature and then the two phases are mixed. A laboratory beaker containing a hot emulsion cools fairly rapidly to room temperature, but a production tank filled with hundreds of gallons of hot material cools more slowly unless external means of cooling are used. This is one reason why the simple transfer of a laboratory process to production requires extensive studies of the cooling and agitation schedule.
- It is advisable to use jacketed equipment for the large-scale preparation of emulsions, so that the heating and cooling cycles can be carefully controlled.
- In the preparation of anionic or cationic o/w emulsions, it is customary to add the oil phase to the water phase, although some technologists prefer the inversion technique, i.e. addition of the water phase to the oil phase.
- In the case of nonionic emulsions, which exhibit a PIT, the inversion technique is not required since temperature alone can be used to control this stage of emulsification.
- If soap is used as the emulsifier, it is usually prepared in situ by combining the alkali with the water phase and the fatty acid with the oil phase.
- Oil-soluble emulsifiers are commonly added to the oil phase, whereas the water-soluble emulsifiers are dissolved in the aqueous phase. Occasionally, it may prove advantageous to include even the water-soluble emulsifier in the oil phase.
- In the preparation of w/o emulsions, it is almost always necessary to add water slowly to the oil/emulsifier blend.
- To avoid losses, volatile flavours or odours are preferably added at the lowest temperature at which incorporation into the emulsion is possible (usually 55–45°C).
- If a gum is used, it should be completely hydrated or dissolved in the aqueous phase before the emulsification step. If a heat-sensitive gum is used, it may be necessary to incorporate the gum solution after the emulsion has been formed. The use of two different organic gums can cause incompatibility.
- It is also noted that anionic and cationic emulsifiers in about equimolar quantities rarely yield satisfactory emulsions.
- It is recommended that parenteral emulsions, especially those designed for intravenous injection, be homogenized until a satisfactory particle size is achieved.
- Since the use of conventional preservatives is contraindicated, such preparations require sterilization at high temperature but must still yield acceptable emulsions after this heating/ cooling cycle.
- Whenever an emulsion is formed at elevated temperatures, the loss of water due to evaporation must be made up. This is done best by adjusting to ‘final weight’ with water when the emulsion reaches about 35°C.
Foaming During Agitation – During the agitation or transfer of an emulsion, foam may be formed. Foaming occurs because the water-soluble surfactant required for emulsification generally also reduces the surface tension at the air–water interface. To minimize foaming, emulsification may be carried out in closed systems (with a minimum of free air space) and/or under vacuum. In addition, mechanical stirring, particularly during the cooling of a freshly prepared emulsion, can be regulated to cause air to rise to the top. If these precautions fail to eliminate or reduce
foaming, it is sometimes necessary to add foam depressants (antifoams); however, their use should be avoided, if at all possible, since they represent a chemical source of incompatibility. Sometimes the use of ethyl alcohol accelerates the coalescence of foam on the surface of emulsions. On the other hand, the most effective defoamers are long-chain alcohols and commercially available silicone derivatives, both of which are generally believed to spread over the air–water interface as insoluble films.
Multiple choice questions:
1.Which of the following are emulsification techniques?
a)Conventional method
b)Condensation method
c)Phase inversion technique
d)All of these
2.Usually, the breakup of the internal phase (by physical means) is fairly rapid; however, it is believed that the stabilization step and the rate of coalescence are time and temperature dependent.
a)true
b)false
3.The application of energy in the form of _____ is required to reduce the internal phase into small droplets.
a) heat
b)mechanical agitation
c)ultrasonic vibration
d)all of these
4.Equipments available to affect droplet breakup and emulsification either in the laboratory or in production are
a)mechanical stirrers
b)homogenizers
c)ultrasonifiers
d)all of these
5.Mixing of immiscible liquids on a small scale is carried out by
a)Conventional method
b)Condensation method
c)Phase inversion technique
d)Low-energy emulsification
6.Emulsifier is triturated with the oil in perfectly dry porcelain mortar then water is added at once in
a)Dry Gum Method
b)Wet Gum Method
c)Condensation method
d)a and b
7.Trituration of gum with water in a mortar to form a mucilage oil is added slowly in portions and the mixture is triturated in
a)Dry Gum Method
b)Wet Gum Method
c)Condensation method
d)a and b
8.In which method of emulsification emulsions are prepared by passing the vapour of a liquid into an external phase that contains suitable emulsifying agents?
a)Dry Gum Method
b)Wet Gum Method
c)Condensation method
d)Spontaneous emulsification
9.The temperature at which the inversion occurs depends on emulsifier concentration and is called
a)phase inversion temperature
b)HLB temperature
c)phase transition temperature
d)a and b
10.All of the internal phase, but only a portion of the external phase, is heated in
a)Phase inversion technique
b)Low-energy emulsification
c)Condensation method
d)Spontaneous emulsification
11.An emulsion is formed without the application of any external agitation in
a)Phase inversion technique
b)Low-energy emulsification
c)Condensation method
d)Spontaneous emulsification
12.In routine production, it is customary to prepare emulsions by a batch process using
a)kettles
b)agitators
c)both of these
d)none of these
13.It is advisable to use jacketed equipment for the large-scale preparation of emulsions, so that the heating and cooling cycles can be carefully controlled.
a)true
b)false
14.Oil-soluble emulsifiers are commonly added to the water phase, whereas the water-soluble emulsifiers are dissolved in the oil phase.
a)true
b)false
15.To minimize foaming, emulsification may be carried out in
a)closed systems
b)under vacuum
c)open systems
d)a and b
Solutions:
- d)All of these
- a)true
- d)all of these
- d)all of these
- a)Conventional method
- a)Dry Gum Method
- b)Wet Gum Method
- c)Condensation method
- d)a and b
- b)Low-energy emulsification
- d)Spontaneous emulsification
- c)both of these
- a)true
- b)false
- d)a and b
References:
- Gaurav K. Jain Theory and Practice of Physical Pharmacy, 1st edition 2012 Elsevier, page no. 233-237.
- Remington Essential of Pharmaceutics, 1st edition 2013, page no. 385-388.
- Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems, 10th edition, page no. 470-475.
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