FORMUROL
Report of the Council on Pharmacy and Chemistry
Formurol, Citrocoll and Aspirophen were submitted to the Council by the Cellarius Company of San Francisco. The manufacturers having failed to substantiate the claims they make for these products, the Council has voted that the preparations be refused recognition. The Council also authorized the publication of the following report, which deals particularly with one of the preparations—Formurol.
W. A. Puckner, Secretary.
Formurol is the product of the Chemische Fabrik Falkenberg, Falkenberg-Gruenau, near Berlin, Germany. The Cellarius Company, San Francisco, acting as selling agents for the United States, submitted Formurol (along with Aspirophen and Citrocoll, also made by the same firm) to the Council, with the statement that it is “hexamethylentetraminsodium-citrate,” and that it has the following composition: “C6H7O7Na.C6H12N4.”
Zernik,[46] who examined these products, reported that Aspirophen, Citrocoll and Formurol do not have the composition that is claimed for them by the Fabrik Falkenberg. Formurol, he states, is not a definite chemical compound, but a mixture of hexamethylenamin and sodium citrate. The agents were advised of this fact by the Council and were asked to submit evidence to substantiate their claims. No such evidence was submitted.
Since a compound having the composition that is claimed for Formurol is theoretically possible, the Council requested that the product be examined in the Association Laboratory to determine whether it still was the simple mixture reported by Zernik, or whether, perhaps, it now possessed the formula claimed for it. The following report was made by the Association chemists:
Formurol, as submitted to the Council, was in the form of tablets weighing about 1 gm. each and appeared to be composed of a fine white substance interspersed with some transparent particles. The tablets were readily soluble in water, were odorless and possessed a slightly acid taste. The aqueous solution responded to tests for hexamethylenamin, citrate and sodium. To determine whether hexamethylenamin was present in the free or the combined state, the method of Zernik was employed. This consists in the extraction of Formurol with chloroform, which dissolves out hexamethylenamin, leaving insoluble sodium citrate. As the use of the solvent, chloroform, would seem to preclude decomposition of such a hypothetical compound as “hexamethylenamin-sodium-citrate,” the extraction of hexamethylenamin from Formurol may be taken to demonstrate its presence in the free state.
That Formurol is not a compound of hexamethylenamin, but a mixture of hexamethylenamin and sodium citrate, was further indicated by the appearance of the crushed tablets described above. Further, on the low-power microscope the powder was found to be composed of transparent crystals and white opaque particles which appeared to be masses of minute crystals. When treated with chloroform the transparent crystals dissolved, leaving the white masses intact, demonstrating the presence of two distinct substances, one soluble and the other insoluble in chloroform. It having been demonstrated that the residue obtained by evaporation of chloroform could not be weighed as hexamethylenamin, due to enclosed chloroform, the amount of this substance in the residue was determined.
The method used has been described in the Report of the Chemical Laboratory of the American Medical Association, Vol. I, p. 55, and depends on the decomposition of hexamethylenamin by means of sulphuric acid to form ammonium sulphate and formaldehyd. From this solution the ammonia is liberated, distilled and determined by titration and from the ammonia found the amount of hexamethylenamin is calculated. By this method Formurol was found to contain (a) 35.42 per cent. and (b) 35.32 per cent., or an average of 35.37 per cent. hexamethylenamin. The residue insoluble in chloroform was shown to consist essentially of disodium hydrogen citrate by determining the amount of sodium (Na) contained in Formurol. The percentage of sodium calculated from the amount of sodium sulphate found was (a) 11.38 per cent. and (b) 11.20 per cent., or an average of 11.29 per cent., equivalent to 62.50 per cent. disodium hydrogen citrate.
As a check on this determination, the amount of material contained in Formurol which is insoluble in chloroform was determined. It was found to be (a) 63.23 per cent. and (b) 63.49 per cent., making an average of 63.36 per cent., and thus agreeing fairly well with the results obtained when the sodium content was assumed to be disodium hydrogen citrate. From this analysis it appears that Formurol is not a definite compound of hexamethylenamin and sodium citrate, but instead is a mixture of these substances consisting approximately of hexamethylenamin 35.37 per cent. and sodium acid citrate (disodium hydrogen citrate) 63.36 per cent., practically a mixture of 1 part hexamethylenamin and 2 parts sodium acid citrate. These results agree with those reported by Zernik[47] and show that the product now, as then, is not true to claims.
In view of the findings of the laboratory, it is recommended that Formurol be refused recognition. As the exploitation of well-known remedies under false and misleading names is detrimental to the progress of medicine, it is recommended that publication of this report be authorized.
[Editorial Note: This report illustrates once more the value of the Council on Pharmacy and Chemistry and the Chemical Laboratory to the medical profession. Before the Council was organized there was no agency to protect the physician’s interests in the matter of pharmaceuticals. Under the old régime Formurol would have been heralded as a new “synthetic” of the most approved made-in-Germany type—and the claims would have gone unchallenged. To-day its status is made clear and the profession is informed. Only those who have closely studied the question can realize what a wonderful power for commercial probity the Council has proved. Under the laissez faire system of the past, many large pharmaceutical firms gave little attention to the accuracy of the claims made for their products. If the advertising gave good “pulling” results, that was all that was asked or expected. Within the past five years a wonderful change has taken place in this regard, and firms of the better class have so modified their advertising as to make it not only conservative in tone, but to approximate scientific accuracy.]—(From The Journal A. M. A., Jan. 21, 1911.)