An Examination of Commercial Fluid Extracts.
By Frederick W. Haussmann.
Every pharmacist who has handled fluid extracts obtained from different manufacturers, must have noticed the variation in their physical properties, as pertaining to color, odor and taste, and also as shown in their miscibility with water or other liquids.
These variations, which were in a number of instances of a striking nature, induced the writer to make a series of examinations, not primarily regarding their chemical composition, such as the alkaloidal percentage, but more particularly the menstruum, as compared with that required by the Pharmacopoeia, and also to determine the causes which led to the differences mentioned in their physical properties.
The first feature to which our attention is called, lies in the various shades of color which are frequently observed in fluid extracts prepared from the same drug.
Due to the high degree of heat at which some fluid extracts are evaporated, variations in odor and taste are also noticeable at times. Extracts whose properties are due to volatile principles, such as buchu, cubeb, eucalyptus, etc., are liable to be affected in this manner.
The physical condition of fluid extracts, as regards their fluidity, varies considerably, and in this respect, as probably in no other, the preparations of some manufacturers are characterized.
Some we find of a decidedly syrupy consistence, especially those with a low alcohol percentage, while others are more approximate to the pharmacopceial products. These variations may be partly due to differences in the physical properties of crude drugs, but in many cases also to the tendency of some manufacturers to economize that most important menstruum constituent, alcohol. Unfortunately, specific gravity is no criterion of the alcohol percentage of fluid extracts.
It is true, that an extract of a high specific gravity, for which the Pharmacopoeia directs a largely alcoholic menstruum, must be regarded with suspicion, but it does not furnish the means to determine the alcohol percentage of the employed menstruum with any degree of accuracy.
While handling a number of commercial fluid extracts, the high specific gravity of some, contrary to his experience with the same official fluid extracts, induced the writer to determine their alcohol percentage.
Taking the menstrua of the Pharmacopoeia as the standard authority, with which the manufacturer, as well as the pharmrcist, should comply, comparisons were made between the alcohol percentage found and that required. The extracts examined were taken at random from the preparations of different firms, and regarded as representing the respective average percentage of their preparations. The following table gives the results obtained:
|Fluid Extract.||Sp. Gr.||Pharmacopoeial Menstruum in Alcohol Percentage by Volume of Official.||Alcohol Percentage Found.|
In the last-mentioned extract, the exact alcoholic percentage of the menstruum cannot be stated, as the Pharmacopoeia directs the drug to be macerated with a mixture of water and glycerin, to be followed by percolation with a mixture of 85 parts alcohol and 15 parts water.
The largest percentage of alcohol in fluid extracts, whose menstruum consists entirely of that liquid, was found in F. E. Cimicifuga, the smallest in F. E. Buchu.
The two samples examined of the latter were from different manufacturers, and a glance upon the table will reveal a decided difference in their respective alcohol percentages. Fluid extracts for which the Pharmacopoeia directs a menstruum of 2 parts of alcohol to 1 of water, contained a comparatively larger alcohol percentage than those for which the same authority requests an alcoholic menstruum of 3 parts of alcohol to 1 part of water. F. E. of Calumba, which belongs to the latter class, was found to contain only 34 per cent. of absolute alcohol, while F. E. Phytolacca, representing the former, contained 51 per cent.
A small alcoholic percentage was also found in a syrupy F. E. Hydrastis.
Remarkable variations were found in fluid extracts with a supposed-to-be diluted alcohol menstruum. The largest percentage found was in F. E. Stillingia, 36 per cent., which is closely approximate to the pharmacopoeial requirement.
F. E. Cascara Sagrada and Taraxacum contained only 12 per cent. of alcohol, by weight.
Compound F. E. Sarsaparilla, with a menstruum of 30 per cent. of alcohol, was found to contain 6 per cent., by weight, while F. E. Glycyrrhiza, with the same alcoholic menstruum percentage, contained 23 per cent.
Glucose in Fluid Extracts.
The syrupy condition of some commercial fluid extracts, and the sweet taste, occasionally observed in preparations from bitter or acrid drugs, induced the writer to determine the percentage of glucose, or, what is perhaps a more correct statement, an allied substance, which likewise has the property of giving the various glucose reactions.
In addition to this, the negative result experienced in some instances, where the preparations were made from drugs, which are not stated to have an appreciable saccharine percentage, or whose sugar, if present, is stated not to possess the power of reducing Fehling's solution, was also the basis for these examinations.
Such was, for instance, found to be the case with several samples of F. E. Gentian, which showed by repeated examination the presence of 5 per cent. of a substance corresponding to glucose in every respect.
According to published authorities, gentianose, the sugar present in gentian root, does not reduce Fehling's solution. This has not been the writer's experience, either in the commercial fluid extract or in a sample which was prepared strictly according to the pharmacopoeial directions. The remarkably high sugar percentage of some fluid extracts prepared from ranunculaceous plant drugs, which, on comparison with similar official fluid extracts, showed a vast difference, was likewise another reason for this investigation.
Glucose is a normal constituent of many plants, also laevulose, or fruit sugar, which possesses likewise the property of reducing Fehling's solution.
In the process of preparation of galenical preparations, it may also be produced by the decomposition of other compounds, such as inulin, triticin, particularly in the presence of heat. These may be regarded as being some of the natural sources of the sugar which is liable to be present in fluid extracts. Again, excessive heat in their evaporation will have the effect of caramelizing some of the constituents, which, however, by careful observation of pharmacopoeial directions, is obviated. Besides this, the claim is made, that caramel is frequently added by manufacturers of fluid extracts on a large scale, for the purpose of coloring their preparations.
The fallacious popular idea that darkness in color is an indication of strength and a criterion of quality is unfortunately also accepted by a number of pharmacists.
Caramel also has the property of reducing Fehling's solution, and forms, in some fluid extracts, when examined for glucose, an important factor.
Glucose cannot be detected with certainty directly in fluid extracts, or liquids containing other vegetable matter. These compounds, as, for instance, tannin, have also the property of reducing Fehling's solution, and must, therefore, first be removed.
The process recommended in Dragendorff's Plant Analysis, precipitation with basic lead acetate, and subsequent treatment with sulphuric acid, was employed.
Ten c.c. of the fluid extract under examination was diluted with water to 20 c.c.
In most cases the mixture became cloudy, and filtration, until a clear liquid was obtained, was necessary.
The mixture was then precipitated with basic lead acetate solution, filtered from the precipitate and the excess of lead in the filtrate carefully precipitated by diluted sulphuric acid.
The liquid, by means of washing the precipitate with water, was made up to the original volume of 20 c.c.
As a rule the effect of picric acid test solution upon the liquid representing 50 per cent. of the fluid extract, was first noted, and also a superficial examination for glucose made by means of the picric acid and potash method of Braun with the intention of determining the necessary degree of dilution before making the volumetric examination with Fehling's solution.
A few statements must be made regarding fluid extracts in general, before quoting the results obtained. In samples containing caramel, if the same is present in considerable amount, the filtrate, after the lead and acid treatment, is of a brown color.
Caramel is not precipitated by basic lead acetate, and through this fact evidence of its presence was shown in a number of fluid extracts.
For instance, in a sample of F. E. Taraxacum, prepared by the writer according to the Pharmacopoeia, the final filtrate, after this treatment, was almost colorless, while in several commercial specimens, similarly treated, the same was decidedly brown. A like observation was also made with F. E. Gentian and several others.
The preparations examined by the writer comprised the products of eight different manufacturing firms, the samples all being selected at random, preferring, however, those official, wherever obtainable.
The amount of glucose, or, perhaps, more appropriately, the substance which reduces Fehhng's solution and gives reactions with other glucose reagents, varied considerably, some extracts showing a high percentage, while others only contained scarcely appreciable traces. Due to lack of time, the percentage was not ascertained in some, while in a number several determinations were made.
The following were the figures obtained:
(1) Twenty samples were examined of this firm, and they are arranged according to the amount of glucose found.
Five per cent. and over. F. E. Taraxacum, Triticum, Gentian and Cimicifuga.
Four per cent. F. E. Cascara Sagrada.
3.5 per cent. F. E. Rheum.
2.5 per cent. Buchu, Prunus Virginiana, Senna, Hydrastis, Asclepias.
One per cent. Grindelia Robusta,
.833 per cent. Humulus and Digitalis,
.5 per cent. Ipecacuanha.
F. E. Belladonna leaves, Calumba and Nux Vomica, also contained sugar in small amount, but no quantitative estimation was made.
F. E. Coca contained less than 0.5 per cent.
F. E. Cubeb, which was also examined, was found perfectly free from all saccharine matter.
(2) From this source 8 samples were examined, quantitative determinations being made in each case.
The largest percentage found was 5 per cent. in F. E. Pulsatilla;
3.5 per cent. was found in Cypripedium;
3 per cent. in Buchu;
2.5 per cent. each in Frangula, Ipecacuanha and Pilocarpus;
.5 per cent. in Rhus Glabra, while the smallest amount found was in F. E. Damiana, namely, .35 per cent.
(3) Five extracts were examined from this source.
The average glucose percentage of these preparations was small, the largest amount being found in F. E. Stillingia, which contained 1.66 per cent., the smallest in F. E. Aconite Root, which only gave indication to the extent of .1 per cent.
F. E. Dulcamara contained about 1.5 per cent.; Belladonna root, 1.25 percent.; and Eucalyptus, .625 per cent.
(4) This source furnished 5 samples.
The largest amount was found in F. E. of Phytollacca, the fruit, which was over 7 per cent.
This is, however, no criterion, as the drug contains considerable fruit sugar.
F. E. Granati Rad. Cortex gave indication of .67 per cent.; Euphorbia pilulifera, .5 per cent.
F. E. Pichi and Quebracho were also examined, and revealed but small amounts, so that a quantitative estimation was not made.
(5) Four samples were examined from this source. The largest percentage was found in F. E. Bryonia, 1.668, per cent., in Hydrangea .712, while in F. E. Xanthoxylum and Lippia Mexicana the exact amount was not ascertained.
(6) Three samples were procured from this source. The largest percentage was found in F. E. Convallaria, which was 2.5 per cent.; F. E. Stigmata Maydis contained 1 per cent., while F. E. Belladonna Leaves showed 5 per cent.
(7) Two samples were obtained from this firm. The largest amount of glucose was found in F. E. Burdock Root, which was 5 per cent. F. E. Pimpinella contained 1.67 per cent.
(8) The two samples from this source were F. E. Coca and Humulus.
The hop fluid extract contained the largest amount, 2 per cent.; the other contained 1 per cent.
A few remarks may perhaps be not inappropriate regarding these determinations.
The remarkably high glucose percentage in some of the representatives of the Ranunculaceae, 5 per cent. each in F. E. Cimicifuga and Pulsatilla, obtained, by the way, from different manufacturers, induced the writer to determine the amount of glucose in F. E. Cimicifuga, prepared by himself.
While traces of glucose were present, determinations by Fehling's solution showed the presence of less than 1 per cent.
The small amount present was also indicated by the fact that Braun's or Boettger's bismuth test, when applied, responded but feebly.
This is remarkable, as the commercial extract examined bore but little evidence of the presence of caramel. (In the pulsatilla sample, the presence of the latter was, however, very evident.)
To determine whether the process of evaporation of the final percolate produced any material change in the glucose percentage found, examination was made respectively before and after the evaporated extract was incorporated with the reserved portion, but no material difference was revealed.
Similar determinations were made with fluid extracts of gentian and rhubarb, with a like result.
Evaporation at the temperature directed by the Pharmacopoeia does not appear to produce any material change—in particular, no appreciable increase of the glucose percentage.
Comparison was also made between fluid extracts, prepared from the same drug and obtained from different manufacturers.
As already stated, considerable variation in color is frequently observable, and this is in many instances due to the presence of caramel.
Regarding their glucose percentage, some variation also exists.
In a sample of F. E. Buchu, the percentage of one sample was 2.5; of another, 3 per cent. The filtrate of the former, after the lead and acid treatment, was almost colorless; of the latter, a decided brown.
In F. E. Belladonna leaves the glucose percentage of one sample was .5 per cent.; of another, less than .2 per cent. Incidentally may be noticed, that the narcotic fluid extracts in general appear to contain but little sugar.
This was observed in F. E. Belladonna leaves, hyoscyamus and also in digitalis.
F. E. Coca leaves, of a deep black color, obtained from one firm, showed a glucose percentage of 1, while the dark green preparation of another firm showed less than .5 per cent
F. E. Humulus, from one firm, strongly alcoholic, precipitating resin on dilution with water, gave indication of about .830 per cent. of glucose, while the dark brown miscible extract from another source indicated 2 per cent.
F. E. Ipecacuanha showed in one instance a percentage of .5; in another, 2.5 per cent.
Other comparisons were also made, but the above may illustrate the claim that commercial fluid extracts, as a rule, are not alike in physical properties and composition as obtained from different manufacturers.
Interesting revelations are made in some fluid extracts after subjecting them to the lead and acid treatment mentioned.
If to the final filtrate picric acid test solution is added, alkaloids, if present in the drug, will be indicated
Among those affected in this manner may be mentioned F. E. Coca, Ipecac, Hydrastis, Quebracho, Cimicifuga, Xanthoxylum, Calumba, and a number of others.
Fluorescent compounds were revealed in the filtrates from F. E. Pichi and Hydrangea, the fluorescence in each being increased by the addition of an alkali.
Comparison was also made between commercial fluid extracts and some prepared from the same drug according to pharmacopoeial directions.
F. E. Cimicifuga has already received mention.
F. E. Gentian readily reduces Fehling's solution, both in the official and commercial preparations.
The samples of the commercial extracts examined, however, showed a glucose percentage of over 5 per cent., while the official preparation was found to contain 2.5 per cent. A like result was also found in F. E. Taraxacum.
This preparation, when made according to the Pharmacopoeia, contained between 2 and 3 per cent. of glucose, while two samples of the commercial fluid extract, showed between 5 and 6 per cent. to be present. The presence of caramel was, however, noticeable in both.
A sample of commercial F. E. Calumba gave ready indication of the presence of glucose, while the preparation made from the drug by the writer was found to be perfectly free from the same. All the available tests for glucose gave a negative indication of its presence.
F. E. Rhubarb, prepared by the writer, was found to contain about 1 per cent. of glucose.
Two commercial samples were found to contain respectively 3 and 4 per cent
A number of similar comparisons were also made, furnishing, in the main, like results.
Incidentally it may also be mentioned that, while making the above examinations, the presence of possible metallic contamination was also inquired into. In a number of commercial samples the presence of copper was easily detected, showing that but little discrimination was used in the selection of the working utensils.
The importance of self-manufacture in this class of preparations cannot be too strongly urged upon the pharmacist, if it is his desire to comply strictly with the Pharmacopoeia.
While it is impossible for him to do so in every instance, there is no reason why he should not manufacture those frequently used, and in whose reliability he can have absolute confidence.
In commercial fluid extracts his only authority is the manufacturer's statement upon the label.