THE AMERICAN

JOURNAL OF PHARMACY

JANUARY, 1899.

ON ACETIC ACID AS A SUBSTITUTE FOR ETHYL ALCOHOL IN EXTRACTING THE ACTIVE PRINCI

PLES OF SOME OFFICINAL DRUGS.

BY EDWARD R. Squibb, M.D., of Brooklyn, N. Y.

(FIRST PAPER.)

In the proposed substitution of acetic acid for alcohol as a menstruum for extracting and a vehicle for preserving and administering the active principles of drugs used in medicine, the very first question is as to the therapeutic equivalency. That is, if the presence of the necessary amount of acetic acid in fluid extracts, etc., can be shown to be therapeutically objectionable, or more objectionable than the necessary amount of alcohol, then it is not proper to make the substitutions.

But acetic acid has long been used for the extraction of cantharides, colchicum, ipecacuanha, opium, squill, etc., without developing any known therapeutical objections, and in a limited experience in the extraction of spices, and of some drugs for veterinary use, it gives extracts practically identical with those from alcohol. The acid has a universally accepted food value, not only as a hydrocarbon, but as a mild acidulous aid in the primary processes of digestion, but in the small quantities that would be present in the doses of fluid extracts, it would be practically inert, or at least as nearly inert as the alcohol which it would replace.

Its properties and value as an antiseptic, deturgent and preservative are well known, but whether it would be present in sufficient

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proportion to preserve such preparations from change during a long time has not yet been determined. The oldest set of samples, made with 10 per cent. acid, are now about two years old and apparently unchanged. Fluid extract of ergot, by the officinal process, is preserved by acetic acid in small proportion, as first proposed and used by Prof. Wm. Procter, Jr., in 1857, and in that case an alcoholic preparation very liable to change has been made per

manent.

Fluid extracts made with acetic acid menstrua are much more loaded with inert extractive matter than when made with alcohol; and this is a disadvantage, but hardly hurtful, nor more than an inconvenience occasionally.

In compounding prescriptions the acetic acid menstruum has a slight general advantage over alcohol in the amount of precipitation on dilution and on mixing, and in the character of the precipitates, these being more soluble, and containing less resin and fat and probably less of the active principle. In administration there are similar slight advantages over alcohol in that the dilutions with water at the moment of taking the doses are less muddy and unsightly, whilst the acidulous taste is less disagreeable.

From these considerations and from all that is as yet known, it is claimed that there are no serious therapeutical nor administrative objections to a more extended and more general trial of this proposed substitution, especially by the pharmacopoeial authorities through the Research Committees.

The chief, though possibly not the only reason for a careful consideration of this proposed substitution is economy in the use of alcohol by the use of a cheaper solvent. The alcohol of the U.S.P., 91 per cent. by weight, costs about $2.40 per gallon of 6 pounds. 13 + ounces avoirdupois, or, say, 35 cents per avoirdupois pound -or, say, 77+ cents per 1,000 grammes.

The acetic acid of the U.S.P., 36 per cent., costs about 10 cents per pound, or 22 cents per 1,000 grammes. When diluted to a strength of 10 per cent., which is the strength most frequently required as a menstruum, the cost is less than 3 cents per pound, as against 18 cents per pound for the Diluted Alcohol of the U.S.P., with which this 10 per cent. acid corresponds-the alcohol menstrua costing six times as much as the acid menstrua to accomplish the same extraction.

In order to measure with a fair degree of accuracy the comparative capacity of alcohol and acetic acid for extracting the active principles of drugs, it was proposed to make parallel extractions of the same drug under the same conditions at the same time. In selecting a drug for the first trial, that is most difficult to extract to complete exhaustion, nux vomica was taken. For the extraction. of this important drug the U.S.P. has an excellent formula and process by which the seed is reduced to a powder that passes through a No. 60 sieve-60 meshes to the linear inch-and is percolated to practical exhaustion with a menstruum of about 64.5 per cent. alcohol, to the first part of which a small proportion of acetic acid is added. That is, 500 grammes of No. 60 powder is moistened with 500 c.c. of the alcohol to which 25 c.c. of 36 per cent. acetic acid has been previously added, and it is then percolated to exhaustion with the alcohol without further addition of acetic acid. This powder and menstruum were used on one series of percolations in competition with a 10 per cent. acetic acid on a very coarse powder in a corresponding series of percolations. The weight of 100 c.c. at about 23° C. of the U.S.P. menstruum with acetic acid was 88.70 grammes-without the acid 88.00 grammes, and the same volume of the acetic acid menstruum at the same temperature weighed 101:43 grammes. The percolates were received in 100 c.c. fractions in narrow-neck flasks, and weighed at about this temperature, and the weights of the menstrua subtracted from the weights of the percolates gave the series of differences that are shown in the table. to indicate the rates of exhaustion.

About 10 kilogrammes of good, well-seasoned nux vomica was taken from a lot of 2,300 pounds and very coarsely ground so that all of it was passed through a No. 9 sieve. Then half of this was powdered and all passed through a No. 60 sieve for the U.S.P. percolations, thus making sure that the fine and coarse were as nearly alike as practicable. Then each portion, fine and coarse, was carefully assayed, the powder giving 2.80 per cent. of mixed alkaloids, and the ground giving 2'93 per cent. of mixed alkaloids; and therefore 1,500 grammes of the powder would contain 42.00 grammes of alkaloids and the same quantity of ground would contain 43.95 grammes of mixed alkaloids, to be washed out by the different menstrua.