Preparation of chloroform water and peppermint water

Home > Pharmacy Information Pointers> Preparation of chloroform water and peppermint water

Pharmacy Information Pointers index

Preparation of chloroform water and peppermint water

Recently, the Royal Pharmaceutical Society's fellow in pharmaceutics, Dr Colin Cable, has dealt with several enquiries from members regarding the preparation of chloroform water and peppermint water. Outlined below are methods for preparing these products, plus information about related preparations.

Further information on this and other pharmaceutics topics can be obtained from Dr Cable (tel 020 7572 2302; e-mail colin.cable@rpsgb.org).

Chloroform water

Chloroform has been used for many years as a preservative for oral liquid pharmaceutical preparations. As a preservative, it is included in most products at a final concentration of 0.25 per cent v/v, although in preparations having a high content of dissolved solids a lower concentration, 0.15 per cent v/v, may be necessary to avoid problems with "salting out" of the chloroform.

Chloroform water has traditionally been prepared by adding chloroform (2.5ml) to purified water (to 1000ml) and shaking frequently until the chloroform is in solution.

Double-strength chloroform water Double-strength chloroform water contains 0.5 per cent v/v chloroform. It is prepared in the same manner as chloroform water by adding 5ml chloroform to purified water (to 1000ml). Double-strength chloroform water requires to be diluted 1:1 by volume. This is usually achieved during the extemporaneous preparation of an oral liquid, to provide a final chloroform concentration of 0.25 per cent v/v (ie, single-strength chloroform water).

Concentrated chloroform water Concentrated chloroform water (BPC 1959) uses ethanol as a cosolvent to permit the preparation of a solution containing 10 per cent v/v chloroform.

If a preparation equivalent to double strength chloroform water is required (ie, a solution containing 0.5 per cent v/v chloroform), one part of the concentrated chloroform water should be diluted with 19 parts of purified water (1 in 20 dilution); this must be further diluted 1:1 to produce a product with a final chloroform content of 0.25 per cent v/v.

To produce a solution having an equivalent strength to chloroform water (ie, one that contains 0.25 per cent v/v chloroform), one part of concentrated chloroform water should be diluted with 39 parts of purified water (1 in 40 dilution).

Chloroform water prepared from concentrated chloroform water will have a residual ethanol content of about 1.5 per cent v/v. For the vast majority of patients this level of ethanol will not be a problem. However, it may have implications for patients taking some medicines, and for the use of this preparation in neonates and children.

Chloroform spirit Chloroform spirit is a solution of chloroform (5 per cent v/v) in ethanol (90 per cent). It is used as an ingredient in the extemporaneous preparation of products such as codeine phosphate oral solution BP and liquid paraffin and magnesium hydroxide oral emulsion BP.

Theoretically, a 1 in 20 dilution of chloroform spirit would produce a solution equivalent to single strength chloroform water (0.25 per cent v/v chloroform). However, the chloroform water produced will contain about 4–4.5 per cent ethanol and its use in this manner cannot be recommended.

Peppermint water

Peppermint oil has carminative, antiseptic and flavouring properties and has been included in a range of official and non-official pharmaceutical preparations.

Peppermint water is a saturated solution of peppermint oil (0.05 per cent v/v) in water.

Concentrated peppermint water Like most other aromatic waters, peppermint water is usually prepared by diluting one part of concentrated peppermint water with 39 parts of purified water (1 in 40 dilution), eg, by diluting 2.5ml of the concentrated water to 100ml. However, to enable concentrated peppermint water to contain 2 per cent v/v peppermint oil in solution, ethanol has to be included in the formulation as a cosolvent. This concentration of ethanol is also sufficient to act as a preservative for the preparation. Thus, peppermint water prepared by dilution of concentrated peppermint water will contain a residual amount of ethanol, usually about 1.5 per cent v/v.

Peppermint water is known to support microbial growth and is prone to contamination with Pseudomonas aeruginosa. Neither the peppermint oil nor the residual ethanol in peppermint water is present in sufficiently high concentrations to have effective preservative activity. It has therefore been recommended that peppermint water is prepared under controlled conditions to minimise the risks of contamination and that a limited shelf-life should be assigned to the product.

Antimicrobial preservative systems have been added to peppermint water as a means of extending the shelf-life. They include chloroform (0.25 per cent v/v), bronopol (0.05 per cent w/v) or a combination of methyl hydroxybenzoate (0.2 per cent w/v) and propyl hydroxybenzoate (0.02 per cent w/v).

Concentrated peppermint emulsion Like concentrated peppermint water, concentrated peppermint emulsion also contains 2 per cent v/v peppermint oil. However, in the concentrated emulsion, the peppermint oil is maintained in solution by using the surfactant polysorbate 20 (0.1 per cent v/v) rather than a cosolvent, and the preparation is preserved with chloroform (0.25 per cent v/v). When concentrated peppermint emulsion is diluted with 39 times its volume of purified water (1 in 40 dilution), a preparation equivalent in strength to peppermint water is produced.

Concentrated peppermint emulsion is used as an ingredient in the extemporaneous preparation of kaolin mixture BP, magnesium sulphate mixture BP, magnesium trisilicate mixture BP and compound sodium chloride mouthwash BP, but is not used in the preparation of peppermint water.

Peppermint spirit Peppermint spirit, also known as peppermint essence, contains peppermint oil (10 per cent v/v) in ethanol (90 per cent). It is used as a flavouring agent. Although a 1 in 200 dilution would give a preparation containing the same amount of peppermint oil in peppermint water, the ethanol content would be much lower (less than 0.5 per cent v/v). Rapid dilution of peppermint spirit with water is likely to lead to the formation of oily globules of peppermint oil on the surface of the liquid rather than the preparation of a saturated solution of peppermint oil.