preparation of benzyl benzoate PDF

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The extemporaneous preparation of benzyl benzoate emulsion 25% as according to the BP specification

Abstract Emulsions are vital for a variety of applications including macromolecular discovery and hazardous material handling (Shah Rutesh K, 2008).In the pharmaceutical industry numerous drugs are prepared as emulsions, common emulsions including o/w such as milk and w/o for e.g. butter. O/W emulsions are generally useful for hydrophobic drugs an example is total parental nutrition which makes use of a sterile O/W emulsion to deliver oily nutrients intravenously to patients (BA, FP, 2017). The initiative of this practical was the preparation of benzyl benzoate emulsion using merely emulsifying wax, benzyl benzoate and purified water with the help of a water bath. The preliminary goal was to ensure the final product passed the BP standard. Introduction Emulsions consist of two or more immiscible liquids one of which is dispersed as small droplets within the other. (Shah Rutesh K, 2008) An emulsion has at least two phases, dispersed (internal phase) and continuous (external phase). (BA, FP, 2017) There are three types of emulsions an oil in water emulsion (O/W), water in oil emulsion (W/O) and multiple emulsions (water in oil in water W/O/W). Pharmaceutical emulsions consist of mainly o/w emulsions and w/o emulsions with the latter being multiple emulsions. O/W emulsions are usually used for emulsions designed for oral uses whilst W/O emulsions are used for topical application as they are unpleasant to take orally. Oil in water emulsion contains the oil phase dispersed within an aqueous phase; the aqueous phase makes up 45% of the weight of the emulsion. Water in oil emulsions are formed by dispersing droplets of the aqueous phase within an oily phase. Multiple emulsions are used widely in the cosmetic industry they consist of droplets of an existing (primary) emulsion. (GI Study pack, 2016) Two examples of pharmaceutical emulsions are Oilatum emollient bath additive emulsion and liquid paraffin oral emulsion. (BNF, 2017) An emulsion is different to a suspension as a suspension is a dispersion of a solid within a liquid or gas. In terms of the pharmaceutical industry, a suspension contains solid particles of drug dispersed within a liquid medium that is not readily soluble. An emulsion is also not soluble but it is a dispersion of two or more liquids not solids like suspensions.

Oil in water Emulsion

Oil in water emulsions are non-greasy, less viscous and are easily removable from the skin surface. They are used externally to provide a cooling effect and internally to mask the bitter taste of oil. In terms of drug release, hydrophobic drugs are released quicker from O/W emulsions. Benzyl benzoate is a synthetic compound that is produced from benzoic acid and benzyl alcohol. It is a colourless liquid or white solid with a faint pleasant odour and a sharp burning taste. (Drugs.com Unknown). The therapeutic class is scabicide and the chemical class is benzoic acid. The molecular formula is C14H12O2 and it is declared as being 99.7% of C14H12O2. (British Pharmacopoeia 2017) Benzyl benzoate is an older preparation used for the treatment of scabies. Scabies is a skin infection caused by tiny mites called Sarcoptes Scabei in the outer layers of the skin. (NICE guidelines 2017) The infection is characterised by severe itching and an angry rash. Benzyl benzoate is deadly to the mite but due to its irritant properties, it is less suitable for prescribing and not the first line treatment (BNF 72 2017). The first line treatment for scabies in children is currently Permethrin 5% dermal cream as there is evidence from a systemic review proving permethrin is highly effective at achieving clinical cure of scabies within 28 days of treatment (Nice guidelines 2017). There is also permethrin 1% cream rinse but it is associated with treatment failure. (COX 2000) Based on recommendations from the Cochrane systemic review it was perceived that benzyl benzoate 25% was less effective than permethrin 5% as it required multiple applications over 2-3 days and produced a burning sensation presenting compliance problems in patients. (Nice guidelines 2016). Benzyl benzoate is available as a lotion, soap and an emulsion. It is also available without a prescription and easily accessible. (BNF 72 2016) The principle of this experiment was the extemporaneous preparation of benzyl benzoate application as according to the British Pharmacopeia. The components used in the experiment were emulsifying wax, purified water (Polar) and Benzyl Benzoate (non-polar). The aim was to formulate an emulsion and identify whether an O/W or W/O emulsion was

produced as well as working within the BP specification to make a final product that would have passed the BP. Method Firstly, calculations were performed according to the prescription and the BP monograph. Benzyl benzoate was calculated for 75g and emulsifying wax for 6g.The emulsifying wax was then transferred to a glass crucible and placed above a water bath. Once the emulsifying wax was melted, 75g of benzyl benzoate was slowly added to the wax whilst mixing using a glass rod. Once the mixture of benzyl benzoate and emulsifying wax was mixed thoroughly it was poured into a measuring cylinder (volume was 100ml). Any remaining product left in the glass crucible was poured into another measuring cylinder and purified water was used to make up the volume to 100ml. The third measuring cylinder contained 100ml of purified water to make up the final volume of 300ml.Any remaining product left on the glassware was washed out with purified water to ensure there was not any product remaining to meet the BP standard. The final mixture was poured into a 300ml beaker and stirred well to ensure the mixture had cooled down enough to a point where it was safe to pour into the empty glass bottle. Once it was cool enough 250ml was measured using a measuring cylinder and poured into the glass bottle. The final label was then produced, checked and displayed on the glass bottle. Results and discussion The practical was successful as the final product produced (benzyl benzoate) passed the BP standard. The BP standard was passed because the product was pure in the fact that the glassware used was thoroughly cleaned with purified water to ensure no product was left behind. Furthermore, purified water was used and not just tap water this prevented contaminants from entering the final product. Water is one of the biggest sources of contamination because it is home to the microorganism Pseudomonas Aeruginosa which can cause many types of problems if it were to enter the final product. (Sterility and Asepsis study pack 2017) The final product produced was identified as an o/w emulsion as it was white and nongreasy. The emulsifying wax used provided a base for the emulsion so the non-polar benzyl benzoate and purified water could form an emulsion. (Aulton M.E 2006) The Purified water also acted as an excipient to bulk up the product to produce excess product (300ml) even though the prescription only required 250ml. There were many possible sources of error including the equipment used for instance there were 3 measuring cylinders in the process of transfer from the mixture to the beaker. This made the process lengthy as product could have been easily lost throughout the process. If one measuring cylinder with a max measurement of 300ml was used it would have been more accurate with less product being lost than using the 3 measuring cylinders.

Also, the scales used to measure both the emulsifying wax and the benzyl benzoate were not accurate or reliable for instance with the benzyl benzoate it was difficult to measure a liquid on scales with a weighting of grams. Whilst 6g of the emulsifying wax was required but the weight fluctuated occasionally on the scales by a couple of points (5.9-6.1) making it difficult to get the exact measurements. An additional error is the temperature of the water bath as there was no standard used, so there was a flux of temperature from low to high to ensure the emulsifying wax melted steadily but was not burning. Another error is some product could have been left in the container if not rinsed out with purified water properly making a difference to the percentage yield of the product obtained as well as loss of product. Furthermore, it’s important the glass rod used to mix the emulsifying water and benzyl benzoate was slightly warm if it was cold it could have instantly crystallised the mixture. Another issue with using a glass rod is loss of product since when mixing product was being transferred onto the rod. In terms of improvements, the experiment could have been improved if it was repeated a few times to improve accuracy. For instance, if the experiment was repeated twice the first time would be a practice run as this was a new practical, the first time would provide an idea of what the finished product looks like so the second time it is carried out the results are more reliable. Another improvement would be to use an actual water bath rather than using a heating mantle and a beaker as it was difficult to set the temperature. Furthermore, by using a water bath, the temperature would have been at a standard improving the reliability of the experiment. Moreover, it is important the purified water has to be warm when added to the mixture as the mixture itself has been heated so therefore it will be warm. A cold substance added to a warm substance would instantly make the mixture crystallise. If the purified water was cold the emulsifying wax would crystallise and the process cannot be reversed this would mean the product would fail the BP standard. Conclusion In conclusion, I found the process was quite lengthy as it was important to ensure the preparation does not crystallise at any point as it would fail the BP standard. It is very easy to fail the BP standard as when adding purified water if the water was not warm enough the mixture will crystallise straight away. Furthermore, as I previously stated the experiment could have been improved by repeating the experiment this would have provided a better interpretation of the results obtained. There were also many sources of error within the practical which I have previously discussed showing that it is likely the final product may not have been pure. Overall the benzyl benzoate application 25% emulsion produced was identified as oil in water emulsion and passed the BP standard, therefore, the practical went according to plan.

References

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