Related entry: Fluidextracts
Extraits, Fr.: Extrakte, G.; Extratti, It.; Extractos, Sp.
Extracts, as the term is employed in the Pharmacopoeias, are solid preparations, resulting from the evaporation of the solutions of vegetable principles, obtained either by exposing a dried drug to the action of a solvent, or by expressing the juice from a fresh plant. A distinction was formerly made between those prepared from the infusions, decoctions, or tinctures, and those from the expressed juices of plants, the former being called Extracta, the latter Succi Spissati, but the distinction has been generally abandoned. There is no such essential difference between these two sets of preparations as to require that they should be separately classed, and something is gained in the simplicity of nomenclature, as well as of arrangement, which results from their union.
The composition of extracts varies with the nature of the vegetable, the character of the solvent, and the mode of preparation. The object is generally to obtain as much of the active principle of the plant with as little of the inert matter as possible, though sometimes it may be desirable to separate two active ingredients from each other when their effects upon the system are materially different; this may be accomplished by employing a menstruum which, while it dissolves one, leaves the other untouched. The proximate principles most commonly present in extracts are gum, sugar, starch, tannin, extractive, coloring matter, salts, and the peculiar principles of plants, to which, when an alcoholic solvent is employed, may usually be added resinous substances, fatty matter, and frequently more or less essential oil, gum and starch being excluded when the menstruum is pure alcohol. Of these substances, as well as of others which, being soluble, are sometimes necessarily present in extracts, we have taken occasion to treat under various heads in this commentary. There is one, however, which from its supposed almost uniform presence in this class of preparations, and from the influence it is thought to exert upon their character, deserves particular consideration in this place. We allude to extractive, or, as it is sometimes called, extractive matter.
It has long been observed that in most vegetables there is a substance, soluble both in water and alcohol, which, in the preparation of extracts, undergoes chemical change during the process of evaporation, imparting to the liquid even if originally limpid, first a greenish, then a yellowish-brown, and ultimately a deep brown color, and becoming itself insoluble. This substance, originally called saponaceous matter by Scheele, afterwards received the more expressive name of extractive, derived from its frequent presence in extracts. Its existence as a distinct principle is denied, or at least doubted, by some chemists, who consider the phenomena supposed to result from its presence as depending upon the mutual reaction of other principles. The most important property of extractive is its disposition to pass, by the influence of atmospheric air at a high temperature, into an insoluble substance. If a vegetable infusion or decoction be evaporated in the open air to the consistence of an extract, then diluted, filtered, and again evaporated, and the process repeated so long as any insoluble matter is formed, the whole of the extractive will be separated from the liquid, while the other ingredients may remain. The name of oxidized extractive which has been given to it is incorrect, and Berzelius proposed to substitute for it that of apothem,
synonymous with deposit. According to Berzelius, apothem is not completely insoluble in water, but imparts a slight color to that liquid when cold, and is rather more soluble in boiling water, which becomes turbid upon cooling. It is still more soluble in alcohol, and is freely dissolved by solutions of the alkalies and alkaline carbonates, from which it is precipitated by acids. It has a great tendency, when precipitated from solutions, to unite with other principles, and to carry them along with it, thus acquiring properties somewhat different according to the source from which it is obtained. In this way also, even when the extractive of a plant is itself medicinally inert, its conversion into apothem may be injurious by causing a precipitation of a portion of the active principle, and in practical pharmaceutical operations this change should always, if possible, be avoided. We shall treat of the subject under the several heads of (1) the extraction of the soluble principles from the plant; (2) the method of conducting the evaporation; (3) the proper condition of extracts, the changes they are liable to undergo, and the best method of preserving them.
1. Extraction of the Soluble Principles.
There are two distinct modes of obtaining, in a liquid state, the principles which we wish to extract: (1) by expression alone; (2) by the agency of a solvent, with or without expression.
1. By Expression.—This method is applicable to recent vegetable substances. All plants cannot be usefully treated in this way, as many have too little juice to afford an appreciable quantity upon pressure, and of the succulent a considerable portion do not yield all their active principles with their juice. Succulent fruits, and various acrid and narcotic plants, are proper subjects for this treatment. The plants should be operated upon, if possible, immediately after collection. Battley, of London, recommended that, if not entirely fresh, they should be revived by the immersion of the stalks in water for twelve or eighteen hours, and those only used which recover their freshness by this management. They should then be cut into pieces, and bruised in a stone mortar till brought to a pulpy consistence. When the plant is not very succulent, it is necessary to add a little water during this part of the process, in order to dilute the juice. After sufficient contusion, the pulp is introduced into a linen or canvas bag, and the liquid parts expressed. Brande states that light pressure only should be employed, as the extract is thus procured greener, of a less glutinous or viscid consistence, and, in his opinion, more active than when considerable force is used in the expression. (See Remington's Practice of Pharmacy.) The juice thus obtained is opaque, and usually green, in consequence of the presence of green wax or chlorophyll, and of a portion of the undissolved vegetable fiber in minute division. By heating the juice to about 71.1° C. (160° F.) the albumen contained in it coagulates, and, involving the chlorophyll and vegetable fiber, forms a greenish precipitate. If the liquid be now filtered, it becomes limpid and nearly colorless, and is prepared for evaporation. The clarification, however, is not absolutely necessary, and is generally neglected. Sometimes the precipitate carries with it a considerable portion of the active principle, in which case it should be subsequently incorporated with the juice, when reduced by evaporation to the consistence of syrup. Ether added to the expressed juices of plants enables them to be kept long without injurious change. Lepage, of Gisors, France, has kept the juice of belladonna in this way more than ten years, and found it, at the end of that time, to yield an extract identical in physical, chemical, and physiological properties with that obtained from the fresh juice. If this fact is found to be of general applicability, it will be of considerable importance, as enabling the pharmacist to supply himself at pleasure with extracts to be relied on, without reference to the season.
2. By Solution.—The active principles of dried vegetable substances can be extracted only by means of a liquid solvent. The menstruum usually employed is either water or alcohol, or a mixture of the two. Water, on account of its cheapness, is always preferred, when circumstances do not strongly call for the use of alcohol. It has the advantage, moreover, that it may be assisted in its action if necessary by a higher degree of heat than the latter. Tap water is often unfit for the purpose, in consequence of the quantity of its saline matter, which in some instances may exert an unfavorable influence on the active principle, and must always be left in the extract. Rain, or distilled water should be preferred. Alcohol is employed when the principles to be extracted are insoluble or but slightly soluble in water, as in the case of the resins; when it is desirable to avoid in the extract inert substances, such as gum and starch, which are dissolved by water and not by alcohol; when the heat required to evaporate the aqueous solution would dissipate or decompose the active ingredients of the plant, as the volatile oils; when the reaction of the water itself upon the vegetable principles is injurious; and, finally, when the nature of the substance to be exhausted requires so long a maceration in water as to endanger spontaneous decomposition. The aqueous solution requires to be quickly evaporated, as this fluid rather promotes than counteracts chemical changes, while an alcoholic tincture may be preserved unaltered for an indefinite period. An addition of alcohol to water is sufficient to answer some of the purposes for which the former is preferable, and the employment of both fluids is essential, when the virtues of the plant reside in two or more principles, all of which are not soluble in either of these menstrua. In this case it is usually better to submit the vegetable to the action of the two fluids successively than of both united.
Extracts obtained by the agency of water are called aqueous extracts; those by means of alcohol, undiluted or diluted, alcoholic or spirituous extracts. Sometimes the term hydro-alcoholic is applied to extracts obtained by the joint agency of alcohol and water.
Chloroform is frequently used to saturate the water used in making aqueous extracts to prevent fermentation during percolation.
The method of preparing the solution is not a matter of indifference. The drug should be thoroughly bruised, or reduced to a coarse powder, so as to allow the access of the solvent to all its parts, and yet not so finely pulverized as to prevent a ready precipitation of the undissolved or inactive portion. When water is alone employed, it has been customary to boil the medicine for a considerable time, and, if the first portion of liquid does not completely exhaust it, to repeat the operation with successive portions until the whole of the active matter is extracted. This may be known by the sensible properties of the liquid, and by its influence upon reagents. But the boiling temperature produces the decomposition of many vegetable principles, or at least so modifies them as to render them inert, and the extracts prepared by decoction are usually less efficient than those made with a less degree of heat. From numerous experiments upon extracts, Orfila concluded that their virtues were less in proportion to the heat employed. It has, therefore, been recommended to substitute for decoction the process of maceration, digestion, or hot infusion, in the first of which the liquid acts without heat, in the second is assisted by a moderately increased temperature sustained for a considerable time, and in the third is poured boiling hot upon the vegetable matter and allowed to stand for a short period in a covered vessel. When the active principles are readily soluble in cold water, maceration is often preferable to the other modes, as starch, which is inert, is thus left behind; but in many instances the preparation would spoil before the extraction would be completed. By digestion, though the solvent power of water is moderately increased, the advantage is often more than counterbalanced by the increased disposition to spontaneous decomposition. Hot infusion, therefore, is to be preferred where the vegetable substance does not readily yield its virtues to cold water. It has the advantage, moreover, in the case of albuminous substances, that the albumen is coagulated, and thus prevented from increasing the bulk of the extract, without adding to its virtues. A convenient mode of performing this process is to introduce the solid material into a vessel with an opening near the bottom temporarily closed, or into a funnel having a notched cork in its mouth, then to pour on the boiling water, and, having allowed it to remain a sufficient length of time, to draw it off through the opening. This operation may be repeated until the water comes away without any obvious impregnation.
It is always desirable to obtain the solution in the first place as concentrated as possible, so as to prevent the necessity of long continued evaporation, which injures the extract. It is better, therefore, to incur the risk, both when decoction and infusion are employed, of leaving a portion of the active matter behind, than to obtain a very weak solution. When successive portions of water are employed, those which are least impregnated should be brought by evaporation to the strength of that first obtained before being mixed with it.
Sometimes filtering a turbid infusion or decoction, before evaporation, causes the resulting extract to keep better by removing substances which, beside undergoing decomposition, may act as a ferment, and occasion the decomposition of the active matter of the extract.
When alcohol is employed as a menstruum, the vegetable substance should be macerated in it for one or two weeks, and care should be taken that the tincture be as nearly saturated as possible. The extraction may be hastened by substituting digestion for maceration, as the moderate heat employed, while it facilitates the action of the alcohol, has in this case no effect in promoting decomposition, and the influence of the atmospheric air may be excluded by performing the process in close vessels.
Acetic acid has been introduced into use as a menstruum in the preparation of extracts. It is supposed to be a better solvent of the active principles of certain substances than either water or alcohol alone. According to Girolamo Ferrari, the acrid narcotics, such as aconite, hemlock, hyoscyamus, and stramonium, yield much stronger extracts with distilled vinegar than with water, and still stronger with alcohol to which strong acetic acid has been added. (J. P. C., 3e ser., i, 239.) Experiments have shown that strong acetic acid (60 per cent.) is a powerful solvent for the active properties of various drugs, particularly those which contain volatile oils, and in many cases a 10 per cent. acetic acid is an excellent menstruum for making extracts; for these the name acetract has been proposed. (Proc. A. Ph. A., 1897, 416.) E. R. Squibb has used acetic acid largely for extracts. (West. Drug., 1897, 123.)
Ether also is now used to a considerable extent in the preparation of certain extracts. Having the property of dissolving volatile oil and resin, and of evaporating at a temperature insufficient to volatilize the oil, it is admirably adapted for the preparation of extracts from those substances the virtues of which reside in the two principles referred to. An ethereal tincture is first prepared by the process of percolation, and the ether is then allowed to escape by spontaneous evaporation, or distilled off at a very moderate heat. The oleo resinous extracts thus obtained are usually of a thick fluid or semi-fluid consistence. Several of them now rank among the official preparations, in the U. S. P., under Oleoresinae. Acetone is another solvent used much for the same purpose as ether.
The process of percolation has in this country been very advantageously applied to the preparation of extracts, both with water and spirituous menstrua. It has the following great advantages:
- that it enables the soluble principles to be sufficiently extracted by cold water, thereby avoiding the injury resulting from heat in decoction and hot infusion
- that it effects the extraction much more quickly than can be done by maceration, thereby not only saving time, but also obviating the risk of spontaneous decomposition; and
- that it affords the opportunity of obtaining highly concentrated solutions, thus diminishing the injurious effects of the subsequent evaporation.
While thus advantageous, it is less liable in this particular case than in others to the objection of yielding imperfect results if not well performed, for, though an inexpert or careless operator may incur loss by an incomplete exhaustion of the substance acted on, and the extract may be deficient in quantity, it may still be of the intended strength and quality, which is not the case with infusions or tinctures unskilfully prepared upon this plan. In the process of percolation the drug must first be reduced to the proper degree of fineness. The U. S. P. (8th Rev.) gives the following directions.
Fineness of Powder.—The fineness of powder is expressed, in the Pharmacopoeia, either by descriptive words (generally so in the case of brittle or easily pulverizable substances), or in terms expressing the number of meshes to a linear inch of the sieve through which the powder will pass. The corresponding values, in terms of metric measures of length, are added below in parentheses, but it has not been deemed advisable, in this revision, to substitute them in the text of the Pharmacopoeia for those at present in use. The diameter of the wire (gauge number) used in making sieve cloth has an important influence upon the size of the mesh, and it is necessary to specify in each case the thickness of the wire, and it was so specified in the U. S. P. VIII but the U. S. Bureau of Standards, owing to the different standards in use by manufacturers of wire gauze determined to standardize the diameter of the particles of the powders, and the U. S. P. IX provides the following statement: "The fineness of powders and granular substances is expressed, in the Pharmacopoeia, by numbers which originally represented only the meshes per inch of the sieve through which the powders would pass. Fineness, so used, has been redefined below in terms of the maximum diameter of the particles of the powder as measured by the width of the opening of the meshes of the sieves from which they receive their designating numbers. A powder of a specified number must meet the requirements given below for that number of powder, but the larger proportion of it must not pass through a sieve of a lower degree of fineness.
|Number of Powder.||Diameter of Particles.|
|No. 100||Powder has a fineness, in diameter of particles, less than 0.14 millimeter.|
|No. 80 - Very fine powder||Powder has a fineness, in diameter of particles, less than 0.17 millimeter.|
|No. 60 - Fine powder||Powder has a fineness, in diameter of particles, less than 0.23 millimeter.|
|No. 50 - Moderately fine powder||Powder has a fineness, in diameter of particles, less than 0.28 millimeter.|
|No. 40 - Moderately coarse powder||Powder has a fineness, in diameter of particles, less than 0.38 millimeter.|
|No. 30||Powder has a fineness, in diameter of particles, less than 0.54 millimeter.|
|No. 20 - Coarse powder||Powder has a fineness, in diameter of particles, less than 0.85 millimeter.|
|No. 12 - Very coarse powder||Powder has a fineness, in diameter of particles, less than 1.47 millimeters.|
|No. 6||Powder has a fineness, in diameter of particles, less than 3.00 millimeters.|
The degree of fineness defined above shall be such as are determined by sieving' tests made with sieves of the Standard Screen Scale recommended by the Bureau of Standards." U. S.
Percolation, as directed in the U. S. Pharmacopoeia IX, consists in subjecting a comminuted substance or a mixture of substances, contained in a vessel called a percolator, to the Solvent action of successive portions of a liquid termed the menstruum in such a manner that the liquid, as it traverses the powder in its descent to the receiver, shall extract the soluble constituents, and pass from the percolator free from insoluble matter:
"When the process is successfully conducted, the first portion of the liquid, or percolate, passing through the percolator will be nearly saturated with the soluble constituents of the substance treated; and if the quantity of menstruum be sufficient for its exhaustion, the last portion of the percolate will be nearly free from color, odor, and taste, other than those of the menstruum itself.
"In preparations which direct the process of percolation, wherever the expression ( until the drug is exhausted' or a similar phrase occurs, it is to be understood that the term 'exhausted' means the point at which the valuable constituents have been as completely extracted 'as is possible or practical, and this must be determined by the judgment and experience of the operator.
"Percolators.—The following statement with regard to percolators and the process of percolation is given in order to illustrate a method of percolation. It is not intended as compulsory and it is permissible for manufacturers and others to modify the process to suit their needs. The percolator most suitable for the quantities contemplated by this Pharmacopoeia should be nearly cylindrical, or slightly conical, with a funnel-shaped termination at the smaller end. The neck of this funnel-end should be rather short, and should gradually and regularly become wider toward the orifice, so that a perforated cork, bearing a short glass tube, may be tightly wedged into it. The glass tube, which must not project above the inner surface of the cork, should extend from 3 to 4 cm. beyond the outer surface of the cork, and should be provided with a closely fitting rubber tube, at least one-fourth longer than the percolator itself, and ending in another short glass tube, whereby (when it is desired to interrupt the percolation) the rubber tube may be so suspended that its orifice shall be above the surface of the menstruum in the percolator, a rubber band holding the tube in position.
"The shape of a percolator should be adapted to the nature of the drug to be operated upon. For drugs which are apt to swell, particularly when a feebly alcoholic or an aqueous menstruum is employed, a conical percolator is preferable. A cylindrical or only slightly tapering percolator may be used for drugs which are not liable to swell, particularly if difficult to exhaust, also when the menstruum is strongly alcoholic, or when ether or some other volatile liquid is used for extraction. The size of the percolator selected should be in proportion to the quantity of drug extracted. When properly packed in the percolator, the drug should not occupy more than two-thirds of its height. The percolator is best constructed of glass, but, unless otherwise directed, may be made of any suitable material not affected by the drug or menstruum. For hot percolation glass percolators are unsuited, as they are liable to fracture. Metallic percolators in such cases are required.
"The percolator is prepared for percolation by gently pressing a small tuft of purified cotton into the neck, and this may then be moistened by pouring a few drops of menstruum upon the cotton, to facilitate the passage of the first portion of percolate, which is often very dense.
"The Process.—The powdered substance to be percolated (which should be uniformly of the fineness directed in the formula, and should be perfectly air-dry before it is weighed) is put into a suitable dish, sufficient menstruum is poured on, and the powder thoroughly stirred until it is uniformly moistened. The moist powder is then passed through a coarse sieve—No. 40 powders, and those which are finer, requiring a No. 20 sieve, and No. 30 powders require a No. 15 sieve for this purpose. Powders of a less degree of fineness usually do not require this additional treatment after the moistening. The moist powder is now transferred to a sheet of thick paper and the whole quantity poured from this into the percolator. It is then shaken down lightly and allowed to remain in that condition for a period varying from fifteen minutes to several hours, unless otherwise directed; after which the powder is pressed, by the aid of a plunger of suitable dimensions, more or less firmly, in proportion to the character of the powdered substance and the alcoholic strength of the menstruum, strongly alcoholic menstrua, as a rule, permitting firmer packing of the powder than the weaker. The percolator is now placed in position for percolation, and, the rubber tube having been fastened at a suitable height, the surface of the powder is covered by an accurately fitting disk of filtering paper, held in place by a glass stopper or percolator weight, and a sufficient quantity of the menstruum poured on through a funnel reaching nearly to the surface of the paper. If these conditions are accurately observed, the menstruum will penetrate the powder equally until it has passed into the rubber tube and has reached, in this, a height corresponding to its level in the percolator, which is now closely covered to prevent evaporation. The apparatus is then allowed to stand at rest for the time for maceration specified in the formula.
"To begin percolation, the rubber tube is lowered and its glass end introduced into the neck of a bottle previously marked for a quantity of liquid to be received, if the percolate is to be measured, or of a tared bottle, if the percolate is to be weighed; and by raising or lowering this receiver the rapidity of percolation may be increased or decreased as may be desirable. A layer of menstruum must constantly be maintained above the powder, so as to prevent the access of air to its interstices, until all has been added, or the requisite quantity of percolate has been obtained. This is conveniently accomplished, if the space above the powder will admit of it, by inverting a bottle containing the entire quantity of menstruum over the percolator in such a manner that its mouth may dip beneath the surface of the liquid, the bottle being of such shape that its shoulder will serve as a cover for the percolator.
"Unless otherwise directed when the dregs of a tincture, or of a similar preparation, are to be subjected to percolation, after maceration with all or with the greater portion of the menstruum, the liquid portion should be drained off as completely as possible, the solid portion packed in a percolator, as before described, and the liquid poured on, until all has passed from the surface, when immediately a sufficient quantity of the directed menstruum should be poured on to displace the retained liquid, until the prescribed quantity has been obtained.
"Repercolation or Fractional Percolation.—Authority is given to employ, where it may be applicable, the process of repercolation, without change of the initial menstruum. This process is used in Type Process C for fluidextracts.
"Rate of Flow.—It is obvious that the success of the process of percolation largely depends upon the regulation of the flow of the percolate; if this should be too rapid, incomplete exhaustion will result, but if too slow, valuable time may be wasted. The rate of flow for fluidextracts for 1000 Gm. of powder should not exceed ten drops a minute; for official quantities of tinctures and preparations of about the same strength twenty drops a minute, and the word ' slowly' throughout the text is understood to mean a rate of flow corresponding to this; it is evident that the proper rate of flow should vary with the quantity and character of the drug employed and the density of the menstruum.
"Maceration.—Percolation is not suitable for exhausting some drugs, and the process of maceration is employed for some of the tinctures (Aloes, Asafetida, Sweet Orange Peel, Tolu, etc.). Specific directions will be found in the text, and maceration should be conducted preferably at a temperature of from 15° to 20° C. (59°-68° F.)." U. S.
For an account of E. R. Squibb's process of repercolation, see Fluidextracta.
Some prefer the mode of expression to that of percolation. This also is applicable both to aqueous and to alcoholic menstrua. The substance to be acted upon is mixed with the menstruum, cold or hot according to circumstances, and the mixture is allowed to stand from twelve to twenty-four hours. The liquid part is then filtered off, and the remainder submitted to strong pressure, in a linen bag, by means of a common screw press, or other convenient apparatus. Another portion of the menstruum may then be added, and pressure again applied, and, if the substance is not sufficiently exhausted, the same operation may be performed a third time. Frequently only a single expression is required, and very seldom a third. The quantity of menstruum added must vary with the solubility of the principles to be extracted. According to Mohr, the method of expression has the advantages over that of the percolation, that it yields solutions of more uniform concentration, that it does not require the materials to be so carefully powdered, or otherwise so skilfully managed, in order to insure favorable results, and, finally, that it occupies less time.
2. Mode of Conducting the Evaporation.
In evaporating the solutions obtained in the modes above described, attention should always be paid to the fact that the extractive matter is constantly becoming insoluble at high temperatures with the access of air, and that other chemical changes are going on, sometimes not less injurious than this, while the volatile principles are expelled with the vapor. The operator should, therefore, observe two rules: (1) to conduct the evaporation at as low a temperature as is consistent with other objects; (2) to exclude atmospheric air as much as possible, and, when this cannot be accomplished, to expose the liquid the shortest possible time to its action. The injurious influence of atmospheric air is much greater at the boiling point of water than at a less heat, even allowing for the longer exposure in the latter case, and therefore a slow evaporation at a moderate heat is preferable to the more rapid effects of ebullition. Bearing these principles in mind, we shall proceed to examine the different modes in practice. First, however, it is proper to observe that decoctions generally let fall, upon cooling, a portion of insoluble matter, and it is a question whether this should be rejected, or retained so as to form a part of the extract. Though it is undoubtedly in many instances inert, as in that of the insoluble substance formed during the decoction of certain vegetable substances, yet, as it frequently also contains a portion of the active principle which a boiling saturated solution necessarily deposits on cooling, and as it is difficult to decide with certainty when it is active and when otherwise, the safest plan, as a rule, is to allow it to remain.
The method of evaporation formerly resorted to in the case of aqueous solutions is rapid boiling over a fire. The more quickly the process is conducted, the better, provided the liquid is to be brought to the boiling point, for the temperature cannot exceed this, and the length of exposure is diminished. But, where this method is employed, it should never be continued until the completion of the evaporation, for when most of the water has escaped, the temperature can no longer be kept down to the boiling point, and the extract is burnt. The caution, therefore, should always be observed of removing the preparation from the fire before it has attained the consistence of thick syrup, and completing the evaporation, either by means of a water bath, or in shallow vessels at a moderate heat. When large quantities of liquid are to be evaporated, it is best to divide them into portions and evaporate each separately, for, as each portion requires less time for evaporation than the whole, it will thus be a shorter time exposed to heat. But the mode of evaporation by boiling is always objectionable, and should be employed only in cases where the principles of the plant are so fixed and unchangeable as to authorize their extraction by the method of decoction.
Evaporation by means of a water bath, from the commencement of the process, is safer than the plan just mentioned, as it obviates all danger of burning the extract; but, as the heat is not supplied directly from the fire, the volatilization of the water cannot go on so rapidly, and, the temperature being nearly the same, when the water bath is kept boiling, there is greater risk of injurious action from the air. The liquid should be stirred during the process. The use of the steam bath has become very general in this country, as it requires a smaller consumption of fuel, and the heat imparted to the liquid, while sufficient to evaporate it, may be less than 100° C; (212° F.). The apparatus consists of an ordinary boiler, containing water, the vapor of which is conducted through a pipe into the evaporating vessels, communicating with each other by means of iron steam pipes. These vessels have the form of an ordinary copper basin, to the inside of -which is riveted a shallow tinned copper evaporating basin, intended to contain the liquid to be evaporated. The vapor from the boiler circulates between these vessels, and the water into which it condenses is allowed to escape through a steam valve attached to the bottom of each vessel. The liquid to be evaporated is first distributed in two or three basins, but when considerably concentrated, is transferred to a single one, where it is stirred towards the close of the process to hasten the evaporation. The heat applied to the liquid can be easily regulated by the steam valves.
As the heat capable of being applied by boiling water to the evaporating liquid does not exceed 93.3° C. (200° F.), while that by steam can, by a moderate pressure, be increased to the boiling point or beyond it, the evaporation by the latter agency may be much more rapid than by the former, when the pressure is from ten to twenty pounds to the square inch; so that there is a temptation to raise the heat to a degree seriously injurious to the product. Evaporation, therefore, by steam heat always requires caution and a stirring device should be used. The water bath is much less liable to be abused. In this respect the latter method has the advantage.
A good plan of evaporation, though slow, is to place the liquid in a broad, shallow vessel, exposed in a stove or drying room to a temperature of about 37.8° C. (100° F.), or a little higher, taking care that the air have free access in order to facilitate the evaporation. This mode is particularly applicable to those cases in which maceration or infusion is preferred to decoction for extracting the active principles. Berzelius says that we may thus usually obtain the extract in the form of a yellowish transparent mass, while extracts prepared in the ordinary way are almost black, and are opaque even in very thin layers. Even when the liquid is boiled at first, the process may often be advantageously completed in this manner. It has been proposed to effect the evaporation at the common temperature, by directing a strong current of air, by means of a pair of smith's bellows, over the surface of the liquid, and in reference to substances which are injured by heat and not by atmospheric air the plan will be found useful.
Plans have been proposed and carried into execution for performing evaporation without the admission of atmospheric air. The apparatus for evaporation in vacua, now largely used by manufacturing pharmacists, is well calculated to meet this object, at the same time that, by removing the atmospheric pressure, it enables the water to rise in vapor more rapidly, and at a comparatively low temperature.
A convenient plan of excluding the air, though it does not at the same time meet the object of reducing the degree of heat, is to distil off the water in close vessels. Berzelius says that this is the best mode of concentration next to that in vacuo. Care, however, must be taken that the fire be not too long applied, lest the extract should be burnt. The process should, therefore, be completed by means of the water bath.
In the concentration of alcoholic solutions, distillation should always be performed, as not only is the atmospheric air thus excluded, but the alcohol is recovered, if not absolutely pure, certainly fit for the purpose to which it was originally applied. Here also the water bath should be employed, to obviate any possible risk of injury from the fire. When the decoction or infusion and the tincture of the same vegetable have been made separately, they should be separately evaporated to the consistence of syrup, and then mixed together while they are of such a consistence as to incorporate without difficulty. The object of this separate evaporation is that the spirituous extract may not be exposed to the degree of heat, or lengthened action of the air, which is necessary in the ordinary mode of concentrating the infusion or decoction.
In every instance, care should be taken to prevent any portion of the extract from becoming dry and hard on the sides of the evaporating vessel, as in this state it will not readily incorporate with the remaining mass. The heat therefore, should be applied to the bottom and not to the sides of the vessel.
Inasmuch as the yield of extracts is largely dependent on the character of the menstruum used in the percolation, it follows that there must necessarily be a great variation in the strength of commercial extracts. C. H. LaWall has prepared a valuable table giving' the yield of extract by various drugs. (Proc. A. Ph. A., 1897, 414.) For methods of assay, see various official processes.
"Pilular Extracts are solid or semi-solid products prepared by exhausting drugs with appropriate solvents and carefully evaporating the solutions to the proper consistence. These extracts preserve the useful constituents of the drug in a concentrated, relatively uniform and permanent condition, and in a form suitable for medication.
"The solvents or menstrua employed in the preparation of pilular extracts are water, alcohol, or mixtures of these in the proportions stated in the formulas. A few drugs require for their extraction the addition of an acid or an alkali to the solvent. Where alcohol is used in the extraction it may be recovered by distillation.
"In the preparation of pilular extracts the concentration of the solutions should be completed without delay, and undue exposure to heat must be avoided. The limit of temperature for the evaporation, as stated in the formulas, should not be exceeded. In the manufacture of these extracts on a large scale an apparatus for distilling and evaporating under reduced pressure should be used. It is also important that the residue be frequently stirred so as to hasten the evaporation and to obtain a uniform product.
"Pilular extracts are extensively used in pill masses and in ointments and, to facilitate their use in these preparations, the degree of concentration is commonly directed to be that of a 'pilular consistence.'
"Pilular extracts should be protected from exposure to sunlight and air by being kept in tightly-covered glass or earthen-ware containers.
"Powdered Extracts differ from pilular extracts in that they are dry, fine powders. Powdered extracts are often preferred to pilular extracts for general use, because they can be more accurately weighed, more easily dispensed, and more conveniently preserved in tightly-stoppered bottles.
"In the preparation of powdered extracts, it is necessary to use solvents that will extract the active principles of the drugs, and only a minimum amount of the inert substances. Where the drug contains an oily constituent that would be extracted by the menstruum directed, it becomes necessary to adopt in the process of manufacture a method for the separation of this oil so that the product will retain a satisfactory, pulverulent form.
"The concentration of the liquids containing the extractive should be completed without delay and undue exposure to heat must be avoided.
"The limit of temperature as stated in the formulas should not be exceeded, and the use of apparatus for concentrating under reduced pressure is recommended. The final drying of the soft extract can be greatly facilitated by spreading it upon plates of glass or tinned metal and exposing it to currents of warm, dry air. Powdered extracts must be thoroughly dried, powdered and mixed with the diluent and preserved in tightly-stoppered, small, wide-mouthed, amber-colored bottles, and stored in a cool and dry place.
"Alkaloidal standards have been adopted for Extracts that can be reliably assayed. Assay methods are directed for the determination of their strength, and to provide for standardization. When necessary, an inert diluent is directed to reduce the product to the standard. In the official formulas glucose is directed for the diluent in pilular extracts and dried starch and magnesium oxide are directed for powdered extracts, but it is permissible for the manufacturer to use as inert diluents for the latter, sugar, sugar of milk, powdered glycyrrhiza, magnesium carbonate or the finely powdered drug or marc from which the respective extract was made. For the convenience of the prescriber, the standards of strength for the Extracts have been adjusted, wherever possible, so that each bears a definite relation to that of the respective drug of average strength, and a statement of the standard precedes the formula," U. S.
3. Condition and Preservation of Extracts.
Extracts may be prepared of three different degrees of consistence: soft, so that they may be readily made into pills, hard, in order that they may be pulverized, and in a fine, dry powder. The soft extracts always contain a notable percentage of water. In astringent extracts, the evaporation should be carried to dryness. Those obtained from the expressed juices of plants are apt to attract moisture from the air, in consequence of the deliquescent nature of the salts existing in the juice. They are thus rendered softer, and more liable to become mouldy upon the surface. Others, especially such as contain much chlorophyll, harden by time, in consequence of the escape of their moisture, and it not unfrequently happens that small crystals of saline matter are formed in their substance; sodium chloride in small cubes is sometimes found in certain old extracts, having slowly crystallized as they hardened. John Attfield of London, has made a chemical examination of the crystals found in numerous extracts, and ascertained that in a large number they consisted of potassium chloride, and in a comparatively few of potassium nitrate. Potassium chloride was detected in the extracts of belladonna, hemlock, sarsaparilla (compound), colchicum seed, stramonium seed, and aconite; potassium nitrate in the extracts of belladonna, hyoscyamus, and lettuce; and sodium sulphate in extract of stramonium seed. (P. J., March, 1862, p. 448.) The air, moreover, exercises an unfavorable chemical influence over the softer extracts, which are enfeebled, and ultimately become nearly inert, by the same changes which they undergo more rapidly in the liquid state at an elevated temperature. If an extract be dissolved in water, and the liquid be saturated with common salt or any other very soluble salt of difficult decomposition, the greater part of it will be precipitated, in consequence of the insolubility of this class of substances in saline solutions. The precipitate may be again dissolved in pure water.
Abstracts, which were official in the U. S. P., 1880, were not re-introduced in the U. S. P. (8th Rev.), as they did not come into general use; this is unfortunate, as they had many advantages, and are used in certain sections of the country. A description and a typical formula, with comments, will be found in the U. S. Dispensatory, 19th edition, p. 466.
Extracts, in order that they may keep well, should be placed in glazed earthenware, glass, or porcelain jars, and completely protected from the access of the air. This may be effected by covering their surface with a. layer of melted wax, or with a piece of paper moistened with strong spirit, then closing the mouth of the vessel with a cork, spreading wax or rosin over this, and covering the whole with leather or a piece of bladder. The application of alcohol to the surface has a tendency to prevent mouldiness. Should the extract become too moist, it may be dried by means of a water bath; should it, on the contrary, be too dry, the proper consistence may be restored by softening it in the same manner and incorporating with it a little distilled water. Martin proposes to preserve extracts in a soft condition by surrounding the vessel containing the extract by another of larger diameter, which is furnished with a tight cover, the space between the two vessels being filled with crystallized sodium sulphate, which gradually parts with its water of crystallization and prevents the extract from becoming hard and dry.
When extracts which are too soft are subjected to a moderate temperature, fermentation may set in; E. Cocardas describes the various forms of "Penicillium-ferment" which are found in such extracts, and concludes that the ferment causes them to undergo changes similar to those effected by heat—viz., the absorption of oxygen and the disengagement of carbon dioxide. (P. J., 1886, p. 590.)
It is preferable to add a definite weight of the glycerin to the percolate. If it were added to the menstruum, owing to the variation in the yield, of extracts from plants, some would be too soft, and at another time, in the case of a large yield of extract, the quantity of glycerin would be insignificant.
Extracts from recent plants should be prepared at the season when the plant is medicinally most active; a good rule is to prepare them once a year; but the demand for extracts from fresh drugs has declined rapidly of late, as it has been found that properly dried drugs yield extracts of uniform strength.
Powdered Extracts.—These extracts are largely superseding soft extracts for reasons given in preceding paragraphs; the difficulty of making them arises from the injurious influence of heat upon concentrated percolates of organic substances, but by the use of vacuum apparatus, suitable absorptive diluents and care, they should be made successfully.
Some extracts when powdered have a tendency to cohere. According to Geiseler, this may be obviated by the addition of sugar of milk or powdered licorice root, two or three parts of the former and one part of the latter to one of the extract being sufficient for the purpose. (Ph. Cb., 1850, p. 238.) Mohr recommends the following plan of drying and preserving extracts. Take equal parts of powdered licorice-root and of the extract, rub them well together in a mortar, put the resulting' paste into an earthen vessel with a flat bottom, place this in another of iron, a little deeper, containing calcium chloride thoroughly dried by heat insufficient to melt it; then enclose the whole with a cover fitted to the iron vessel, and allow them to stand for a day or more. When the mixture is quite dry, powder it, and add so much of the powdered root as to make the weight double that of the original extract. This process was substantially adopted in the German Pharmacopoeia (1882). The old process of using dextrin as a diluent was found very objectionable, principally on account of the tendency of the extracts to reabsorb moisture. Four parts of extract are now mixed with three parts of finely powdered licorice-root, and dried in a porcelain dish at 40° to 50° C. (104°-1220 F.) until the mixture ceases to lose weight. The mass is then rubbed to powder, and sufficient powdered licorice-root added to make the whole weigh eight parts, or double the weight of extract used. In our opinion, this method is not so good as that formerly adopted for abstracts. The German powdered extracts are always half the strength of the extracts, no relation whatever with the drug is established, and the variations in the yield of extract from different drugs have been repeatedly shown to be great. Kirchmann proposes exsiccated sodium sulphate as a diluent instead of dextrin, licorice-root, etc. (Ph. Ztg., 1881, 116.) A. B. Lyons, of Detroit (1898), has introduced scale extracts. These do not, as a class, bear a definite relation to the drug; they are assayed, however, and acacia is used as a means of preserving their dry condition; they are easily pulverized, and are very convenient for dispensing.
The plan of incorporating a little glycerin with extracts has been recommended for such extracts as require it, 10 per cent. of glycerin being added to the liquid extract before evaporating to a pilular consistence. By its unchangeable liquid character, glycerin keeps the extract soft, so that it can be readily made into pills, and it also exercises a favorable influence through its chemical properties. The U. S. P. (8th Rev.) directs the use of glycerin for this purpose as follows: "When it is desired to preserve a solid extract (for instance, of Gentian, Taraxacum, etc.) in a plastic condition, suitable for making pills, or for other purposes, it is recommended that there be incorporated with it, after it has been evaporated to the proper consistence, and while it is still warm, 10 percent. of its weight of glycerin." U. S.
Eight extracts were dismissed at the last revision of the U. S. Pharmacopoeia, these were as follows: Aloes, digitalis, euonymus haematoxylon, krameria, leptandra, quassia, and scopola; five extracts were added as follows: Aconite, oxgall, gelsemium, hydrastis, viburnum prunifolium.