Tincture Deposits. *
(* Read at a meeting of the "School of Pharmacy Students' Association." February 5, 1885.)
By R. A. CRIPPS.
In November, 1883, I had the honor of reading before the "School of Pharmacy Students' Association" a report upon "Tincture Deposits," by which I mean that sediment which is formed in a tincture after filtration. (See "Amer. Jour. Phar.," 1884, p. 101.)
That report included notices of the following tinctures: Tinct. calumbae, cardam. comp., chloroformi comp., cinchonae comp., cinchonae flavae, ferri acetatis, gentianae comp., ipecac., lobeliae inf. aether., quiniae and rhei, and it was there shown that the deposits in most of these are of little importance; the two cinchona tinctures and that of acetate of iron being exceptions to the rule.
I now purpose to continue that report, giving the results obtained with a few more deposits received since that time.
Tinctura Digitalis.—The deposit from this tincture is of a pale greyish-green color and small in amount. It was first washed slightly with proof spirit, then digested for a short time with dilute acetic acid, and the solution filtered. The filtrate was only slightly colored, it was shaken twice with chloroform, the chloroformic solution removed by a separatory funnel and evaporated slowly to dryness. The residue was then tested for digitalin by the following method: A few drops of strong sulphuric acid were added to the contents of the dish, and the vapor of bromine applied, a slight violet coloration was produced showing the presence of a small amount of digitalin; but it was very small indeed, quite insufficient for estimation, perhaps 5 per cent. of the whole deposit, which from 1 gallon of the tincture weighed barely 20 grains.
Tinctura Ferri Acetatis.—Another sample of this deposit having been sent to me I estimated the amount of ferric oxide it contained; this amounted to 76.44 per cent., showing that the deposit varies in composition, the former sample giving 69.77 per cent. It was similar in appearance to the last, and the quantity obtained from 1 pint was 33 grains.
Tinctura Lobeliae Aetherea.—This deposit was similar in appearance to that previously examined, and like it contained no lobeline, but proved to be a fatty body. It is no doubt formed by the slow evaporation of the ether rendering the fat less soluble. Another sample occurred in crystals, but was of the same nature in other respects.
Tinctura Nucis Vomicae.—The deposit in this case was very suspicious, being white and in feathery crystals. It was carefully washed with rectified spirit, and the following tests applied:
1st. Sulphuric acid and bichromate of potash. No reaction for strychnia, only reduction of chromate.
2d. Nitric acid. Only faint yellow color.
3d. Sulphuric acid and gentle heat, an orange-red color, but scarcely like the loganin reaction of Messrs. Dunstan and Short.
4th. Boiling with dilute sulphuric acid, and action upon Fehling. None.
These results being negative, I proceeded to dry some, and in doing so noticed that it melted and gave a greasy stain to paper; this, together with the production of soap with caustic potash, proved it to be nothing but fat. Its melting point was found to be 117°F. From ½ gallon of tincture only about 5 grains were obtained.
Tinctura Opii.—This deposit was very small indeed, and appeared as little whitish warty masses on the sides of the bottle. They proved to contain neither morphia nor meconic acid.
I have also received some few deposits which, from the very uncertain nature of their active principles, I have been unable to examine; they are tinct. cascarillae, from Messrs. Thresh and Wright, and tinct. cuspariae and sennae, from Mr. Want, of Blackheath. I desire to thank these gentlemen and also others who have sent me these deposits. The remaining tinctures of the Pharmacopoeia either deposit so slightly as to be unimportant and to make the examination of them a waste of time, or the drugs are themselves so little known that any examination is impossible. (I have since received a large deposit from Mr. J. O. Braithwaite which occurred in tinct. hyoscyami, the examination of which will shortly be published.)
From the results I have obtained we see that the tinctures of the British Pharmacopoeia remain practically of the same strength for any reasonable time after preparation; that is, in so far as one may judge from the nature of their deposits, although of course changes may occur in the clear liquid by which the amount of active principle may be either raised or lessened, but this is not probable. It may be said on this account that the present tinctures are a satisfactory series of preparations, and if made from drugs of good quality leave nothing to be desired in point of uniformity. But this is a great mistake, for a drug of good quality in one year may be very much stronger than a similar one in the year following, and even in the same year drugs may vary considerably in power and yet be very similar in physical characters. These statements are borne out by the results of Messrs. Braithwaite and Hogg in the case of cinchona, and by Messrs. Dunstan and Short in the case of nux vomica. These instances are especially selected because those experimenters worked upon the tinctures themselves; but much more might be added if we took the results of experiments upon the drugs. Mr. Hogg found in tincture of cinchona from 0.25 per cent. to 0.58 per cent. of total alkaloids, while Mr. Braithwaite's results showed a variation from 0.279 to 0.49 per cent. of total alkaloids, and from 0.070 to 0.345 per cent. of ether-soluble alkaloids. Messrs. Dunstan and Short have shown that tincture of nux vomica is equally liable to variation. Of twelve samples which they examined the total alkaloids varied from .124 to .360 per cent., while the strychnia ranged from .046 to .131 per cent.
From these figures, and they might be multiplied almost indefinitely, one draws the very natural conclusion that a series of tinctures standardized to a given percentage of active ingredient is a most desirable addition to pharmacy. But one is here met with the difficulty of determining what constituent of the drug shall be considered the active principle. The alkaloids or glucosides are no doubt by far the most potent constituents, but still they do not fully represent the drug, or there would be no need. to use Pharmaceutical preparations at all. There must therefore be some other constituent which modifies the action of the alkaloid, and in most cases this is either unknown or extremely difficult of estimation. This is where analysis fails, and upon this Mr. Schacht has based an argument against standardization. Our present knowledge of drugs, he says, is not sufficiently accurate to justify us in bringing forward such preparations.
But, I ask, are we always to wait till our knowledge is absolutely perfect before we apply it to practical uses? I am afraid that if this were done we should never see the results of any scientific work. Besides, it is a general law of nature that things grow by use; if the child did not use his early power of moving his legs, would he ever learn to walk? If the mind were allowed to run riot and its powers of thought left uncultivated, where would be our mathematicians, scientists or men of business? So with scientific knowledge. Use what we have for practical purposes and it will increase in the use. To apply it to the present case: by the practical working out of methods of titration a deeper knowledge of the constitution of a plant must follow, which will most certainly lead step by step to a thorough knowledge of its more indefinite constituents. The alkaloids alone do not represent the full activity of a plant, but it is fairly well established that a specimen containing 1 per cent. of alkaloid is stronger than one containing only .75 per cent., and therefore the activity of a drug may be measured by that alkaloid, since the other constituents are present in both cases.
This applies when there is but one alkaloid, but when there are two or more, as in cinchona or nux vomica, the difficulty is greater. In these cases it would perhaps be safest to standardize the most powerful to a definite amount; but the remaining alkaloids should also be kept within safe limits by the wise discrimination of drugs. For example, in the case of nux vomica tincture, .08 per cent. of strychnia is the average of Messrs. Dunstan and Short's results; but I think the nux vomica should be so chosen as to keep the brucia within the limits of .10 and .15 per cent., the highest and lowest of Mr. Short's being .24 and .075 per cent. The practical difficulties of dilution, etc., urged by Mr. Schacht against standard extracts, cannot be applied to tinctures, since there can be no objection to a little spirit more or less. Mr. Schacht seems rather to indicate that the medical profession does not call for such preparations. If this be the case I wonder at the use of' the alkaloids at all; why do they not confine themselves to the old-fashioned infusions and extracts? The very fact of the immense use of alkaloids shows plainly that if standard tinctures and extracts are placed before the medical profession they will be largely and readily prescribed. One would scarcely expect a prescription to be written for standard tincture of opium, for instance, until some firm has brought out such a preparation; the patient could scarcely wait while the chemist devised a method for estimating it.
In regard to standard extracts which, like the tinctures, shall be constant in strength, I have not yet had sufficient experience to speak very strongly as to their feasibility, but I hope soon to be able to show that a series of them is not only desirable but also possible.—Pharm. Jour. and Trans., March 21, 1885, p. 769.