Wednesday, March 11, 2015

Emulsions - Part 2

English Method (Wet Method)

The acacia solution is place in a mortar and a small quantity of the oil is added. (The amount of oil to be added at one time depends on the quantity of emulsion being prepared). The pestle is rapidly and lightly rotated, dashing the oil into globules, which are prevented from coalescing by the intervention of the emulsifying agent. It is advisably necessary to add an additional portion of the oil at this point, but as emulsification progresses and the nucleus grows, it will also be necessary to add water occasionally to maintain the proper consistency.

Example of Emulsion using English Method

To prepare 120 ml of a 50% emulsion of cod liver oil the following shall be needed:

Oil                                60 ml
Acacia                            15 g
Purified Water, q.s.  __________
            To make           120 ml

Add 15 ml of water to the acacia to make the mucilage and being adding oil in approximately 2 ml portion, increasing the quantity slightly as the emulsion develops.

The English Method is slower and calls for considerable care and skill and recognition of various conditions which should or may develop in the emulsification process. In this method the emulsifying agent is always used in liquid form, as represented by mucilages of acacia, tragacanth, or chondrus, agar solution, egg yolk, etc. This requires, as in the case of acacia, which preferably used, that thick mucilage is prepared. To make satisfactory mucilage of acacia, granular acacia should be mixed in a mortar with an equal quantity of water added all at once, while stirring with the pestle. This will eliminate lumps and produce smooth mucilage in a very short time. It is advisable to dilute the original mucilage slightly by the addition of a little more water. The amount of oil to emulsified, although a smaller quantity may serve the purpose equally well.

When to add water and when to add oil is a question which must be mastered by those who attempt to use the English Method. It may resolve itself into a case of alternating one with the other but the question depends entirely on how much of either is added at a time. If too much water is added and the emulsion additional becomes too thin, it will be impossible to emulsify additional oil. Like, if insufficient water is added, the emulsion becomes too thick and “cracks” because there is not enough aqueous mucilage to cover the globules of the oil present. The emulsion must be kept of such consistency that the pestle makes a characteristic crackling sound as it spins around the mortar. This crackling sound is due to the thick emulsion, or mucilage stretching out between the sides of the mortar and the pestle, and snapping back as it finally breaks away from one or the other. At this stage the emulsion should be smooth and creamy in appearance and show a high uniform gloss throughout. On the other hand when cracking develops, the emulsion loses its uniform gloss and takes on a “pearly” appearance, showing a definite sheen and evidence of free oil globules. Should this occur, it is often possible to save the emulsion by setting it aside for a few minutes, to allow progress of the separation. Much of the air which has likely been beaten into the emulsion separates and the oil and aqueous phases become more pronounced. If water is now added and the mixture triturated, the emulsion will immediately turn normal. If too little water is found to have been added, trituration should be discontinued, the emulsion set aside for a few minutes then more water added and the mixture triturated. But if too much water has been added the emulsion may become so thin that it will be impossible to emulsify any additional oil. In this case a new mucilage may be prepared and the broken emulsion reclaimed by adding it slowly to the new mucilage. When all of the oily mixture has been incorporated, the emulsion may be brought to its final volume by the addition of water, preferably added in small portions.

It is an accepted fact that the smaller the oil globules, the slower the rater of creaming; thus according to Stoke’s Law – if an oil globule is cut in half, the creaming rate is reduced to one-fourth. Consequently, the longer is the trituration given to the emulsion while in its original thick condition; the better is the finished emulsion.

The Continental Method (4-2-1 Method) or (Dry Method)

When a hand homogenizer is not available the Continental Method is preferred over the English Method because it will produce an emulsion more quickly. The Continental Method has a real merit of never failing to produce a good emulsion if the proportions are maintained in forming the nucleus and if the directions are strictly followed. For olive oil, cod liver oil, and castor oil the proportion must be “one-half as much water as oil, and one-half as much acacia as water” or “4 oil, 2 water, 1 acacia”. This produces only the nucleus although all of the oil is emulsified, so additional water should be finally added to dilute the emulsion to the proper strength. The method consists in the following: - the acacia, in fine powder, is added to the oil and mixed intimately (powdered acacia is the only natural gum which produces a good emulsion by the Continental Method when a mortar and pestle are used). The 2 parts of the water is added all at once, while stirring vigorously with the water and the mucilage thus formed envelops the oil globules which result from the active stirring of the mixture. Considerable skill is required in handling the mortar and pestle at this point. Trituration must be fast and must cover the entire surface of the mortar to maintain until the mixture becomes very thick and a “perfect nucleus” is formed. Then additional water may be added as required.

The powdered acacia should not be triturated with the oils longer than just enough to mix the two intimately. If the oil and acacia are allowed to remain contact any appreciable time, the acacia imbibes the oil.  This causes the oil to dissolve poorly when water is added and interferes with emulsification. Using the Continental Method, it is essential that the acacia dissolves very rapidly when water is added to the oil and acacia mixture. The following factors are very important in producing a satisfactory emulsion using Continental Method:

1. Use of a dry mortar
2. Correct proportion of ingredient
3. Measuring oil in a dry graduate
4. Adding all at once two parts of water
5. Rapid and continued trituration

The pestle should be lightly held between the thumb and the first two fingers and it should be rotated entirely by a finger and wrist motion to obtain the speed which is highly essential. The head of the pestle should be forced against the curve of the mortar and not rotated with a purely circular motion in order to produce a shearing action on the oil globules.

In making Continental emulsions of some oils, other than standard cod liver oil or castor oil type, it is a necessity to change the proportions of the ingredients. In case of oil of turpentine the proportion is “3 oil, 2 water and 1 acacia”. For liquid petrolatum the proportion is “2, 2 and 1”.

Addition of Salt, Syrup and other ingredients:

It is a general rule that when salts, syrups (as flavoring) and alcohol (preservative) are to be added to emulsions, they should be dissolved in or diluted with water before adding to the emulsion. Salts ionize in solution and if carelessly added to the emulsion, they will neutralize the charge on the dispersed phase and cause the oil globules to coalesce. If salts are added in concentrated solution, they may break the emulsion by a dehydration process, taking water away from the interface. Syrup added in a concentrated form may cause emulsion to break due to dehydration at the interface.

If an ingredient in an emulsion prescription of formula is soluble in a substance which is to become the inner or dispersed phase, it should be dissolved in that substance first before any attempt is made to make emulsion.

Hand Homogenizer

Hand Homogenizer in small scale production may be used for preparing either O/W or W/O emulsions. In both instances, the technique is the same. The water-soluble ingredient and the oil-soluble ingredients are combined separately, using appropriate technique to obtain a solution in each case. These two phases are shaken together in a bottle or otherwise thoroughly mixed and the rough emulsion which forms is pumped through the homogenizer several times. The hand homogenizer eliminates all failures due to faulty techniques. If unsatisfactory emulsion results the fault usually will be found in the formula employed.

Special Emulsions

1. Transparent Emulsions – known also as Micro-emulsions, are clear, colloidal dispersions of one liquid dispersed in another. The resultant emulsion is clear because the particle size of the dispersed phase is probably in the range of 100 – 600A. Some uncertainty still exists as to the demarcation line between micro-emulsion and clear dispersion brought about by micelle formation (solubilization). Unfortunately, no exact methods are presently available to distinguish solubilized oil from one which can be called micro-emulsions.

According to Osipow there are 3 important aspects of micro-emulsion theory:

(a) The combination of emulsifying agents and their concentration must be such as to produce a metastable negative interfacial tension.
(b) The emulsifier interphase must not be too highly condensed.
(c) The molecules of the oil phase must be able to interpenetrate or associate with the mixed interfacial film constituting the interphase.

One of the chief advantages of micro-emulsions is that they are thermodynamically stable; no emulsifying equipment is needed to produce the emulsion. It is very important that the emulsion formula be designed in such a manner that the micro-emulsion will be formed.

2. Gum-Resin Emulsions – these are prepared from asafetida, ammoniac, etc. which are usually misnamed since they are not true emulsions but suspensions. To prepare them, the materials are crushed and only a small portion of water added at first, just sufficient to make a heavy paste. When this becomes uniform, additional water is gradually added with constant stirring.

3. Seed – Emulsion – This is made by triturating oil seeds such as almond seeds in water. They are examples of emulsions prepared without added emulsifying agents, since all the ingredients necessary for emulsification are in the seeds themselves. Preparation is the same as the gum – resin emulsions.

4. Emulsions of Phenyl Salicylate (Salol) – this type of emulsion may be compounded by dissolving the salol in the oil with the aid of a little heat and then proceeding in the usual manner to make an emulsion.

5. Emulsions of Volatile Oils – an example of emulsions of volatile oils is the Turpentine Oil Emulsion which is made by the Forbes’ Method. This is suitable for oils particularly volatile oils which are capable of being dispersed as minute globules by shaking in a bottle. In another common method of emulsification the volatile oil is mixed with a bland fixed oil, the latter imparting sufficient viscosity to the mixture to allow use of the regular continental method.

Emulsions may be intended for: (1) oral use (2) parenteral use and (3) external use.

Emulsions for Oral Use:
This kind of emulsions should contain ingredients which have been proved by both animal and clinical experience to be safe. There should be adequate testing for the safety of the final product. Legal requirements with respect to stability of the active ingredients and of the final product may require further testing. Most oral emulsions will require one or more flavoring agents to improve the palatability of the product. Flavors should be considered from the standpoint of possible long-term use of the product. In general, the flavor or blend of flavors should be dissolved in the aqueous phase, but there are instances where it might be advantageous to have the flavor in the oil phase, as for instance with very distasteful oils. All oral emulsion products should be in such manner that the product will remain free of the effects of bacteria, molds or yeasts. This is particularly important for emulsions which contain gums and similar organic substances. An extremely efficient preservative in emulsion products is alcohol in 10 – 15% concentration. Other chemical agents useful as preservatives are: benzoic acid (0.2%), parahydroxybenzoates (0.1 -0.2%), sorbic acid (0.2%) and benzalkonium chloride (0.1%).

Antioxidant and buffers may be incorporated into the emulsion product for a specific purpose and should be selected as judiciously as preservative agents.

Emulsions for Parenteral Use:
Oil – in – water (O/W) emulsions develop suitable intravenous preparations for a number of specific clinical uses. By far the most important use made of emulsions is the incorporation of fats and oils with high caloric contents in preparations to be administered intravenously to patients who cannot ingest food and by the other routes. The emulsion must be non-toxic, sterile and pyrogen-free. Some parenteral emulsions are used for diagnostic purposes – example, contrast medium.

Emulsions for External Use:
All external emulsion products, whether for therapeutic or cosmetic use, must be esthetically acceptable. It is very important to consider the texture, aroma, staining characteristics and color, since these may mean the success of failure of the emulsion.

Packaging of Emulsion

There are three considerations for choosing packaging for emulsions.
1. Esthetic quality of the final package
2. Protective effect of the package on the product
3. Utility of the package to the user

It is necessary that packaging materials should be one which will not release a constituent into the emulsion system nor sorb one or more of the ingredients.

Example of Emulsion

Liquid Petrolatum Emulsion, NF

Other Names: Emulsum Petrolati Liquidi; Mineral Oil Emulsion and Liquid Paraffin Emulsion

Mineral Oil                   500 ml
Acacia, v.f.p.                 125 g
Syrup                            100 ml
Vanillin                          40 mg
Alcohol                          60 ml
Purified Water, q.s.     _________
          To make              1000 ml

Mix the mineral oil with the powdered acacia in a dry mortar, add 250 ml of purified water all at once, and emulsify the mixture. Add in divided portions, triturating after each addition, a mixture of syrup, 50 ml of purified water and the vanillin dissolved in the alcohol. Then add sufficient quantity of purified water to make the product measure 1000 ml and mix well.

Uses: Intestinal lubricant and cathartic.

Dose: Usual is 30 ml.

Note: Other methods of emulsification may be used and the quantity of acacia may be reduced or replaced by agar, gelatin, tragacanth or mixtures of any of these provided the resulting emulsion is similar in viscosity and appearance to the emulsion made by the given formula. Vanillin may be replaced by not more than 1% of any other official flavoring substance or mixture of official flavoring substances. 60 ml of sweet orange peel tincture or 2 g of benzoic acid may be used as preservative in place of the alcohol.