preceding operation after the first 3 fluidounces had passed, and percolate again in the usual manner, using the several reserved percolates, successively, as menstrua. Set aside the first five (5) fluidounces, and continue the percolation until ten (10) fluidounces more have passed, which should also be received in several portions. Finally moisten the third portion of the drug (3 troy ounces) with the most concentrated of the last reserved percolates, and proceed as directed for the second portion. Collect the first eight (8) fluidounces separately, and mix them with the two portions previously set aside so as to make sixteen (16) fluidounces of Fluid Extract.

This process is adapted for the preparation of solid as well as fluid extracts, but not for other pharmaceutical preparations made by percolation.

This process yields a perfect fluid extract without the use of heat, thereby adapting it to the most sensitive drug. It recommends itself to the apothecary, in that it avoids the loss and expense caused by subsequent concentration; it nearly always insures a perfect preparation, because, though it be indifferently applied, the inaccuracies of one operation are likely to be made up and compensated in others, so that, when the results of the different percolations are mixed together, the general result will be practically uniform.

The only disadvantage the process offers, is that it necessitates the keeping of a series of weak percolates which must be stored away, to be used for the same drug in a subsequent operation.

PERCOLATION AND MACERATION WITH EXPRESSION.

These methods are employed principally by manufacturers on the large scale. The first method consists of a combination of percolation with expression. One hundred parts of the drug are moistened, packed, and allowed to macerate several days in a percolator; percolation is then commenced and continued, until 120 parts of menstruum have been added, then when the percolation ceases, the upper stratum, constituting about one-fifth of the drug, is removed and subjected to powerful pressure; the fluid obtained is poured over the balance of the moist drug in the percolator, and when this again ceases to percolate, a second like portion is removed and treated as before; this procedure is continued until the entire amount of drug has been expressed. The reserved percolates are mixed with the fluid obtained from the last expression, making a total of 95 parts of fluid extract.

The second method is simply that of maceration and expression, in which the drug is allowed to macerate from 10 to 12 days with about its own weight of menstruum. The maceration is conducted in a tight cylindrical copper vessel, which is inverted at intervals to facilitate the action of the solvent. At the end of the specified time, the drug is removed and subjected to powerful pressure; the marc is returned to the macerator and sufficient

menstruum is added to make up the desired yield. The products of the two expressions, when mixed, constitute the fluid extract.

MACERATION AND PERCOLATION IN VACUO.-As already explained (page 206), the principle underlying this process is this: that, by exhausting the air from the drug, the menstruum is rapidly brought into intimate contact with the cells of the drug, whereby the maceration and exhaustion is expedited. This form of apparatus has been adopted by some of our manufacturers for the preparation of Fluid Extracts. The advantages claimed are that it can be very economically operated, requiring only 16 fluidounces of menstruum for the exhaustion of each pound of drug, besides avoiding much loss of alcohol; and also economizing time. No class of pharmaceutical preparations has met with so much favor as the fluid extracts. They certainly deserve their popularity, for (if properly prepared) they fully represent all of the active properties of the respective drugs, in a compact form. Aside from this, they present another advantage over the tinctures, namely, this, that owing to their concentrated form, they contain a proportionally much smaller amount of alcohol, the presence of which is a serious objection in such preparations as tincture of conium or of digitalis, for the medicinal action of these drugs is considerably counteracted by the antidotal effects of the excess of the alcohol present.

PRESERVATION.-Fluid Extracts should be kept from the direct rays of the sunlight, and in a room where there is but little variation of temperature. These precautions should be observed so as to avoid changes that may arise from possible precipitation, which, however, cannot be altogether avoided.

The various causes which give rise to precipitates in fluid extracts are, according to the researches of Lloyd:*

1st. Oxidation.-Many vegetable principles are prone to unite with oxygen, forming thereby new and insoluble compounds, which, on being precipitated, carry more or less of the active constituents with them.

Again, an interaction between the plant principles may take place, either gradually or suddenly, with the formation of new or insoluble bodies.

Fluid extracts of astringent drugs, such as geranium, stillingia, cinchona, etc., which contain large amounts of tannates, especially drugs containing red tannates, form, in time, precipitates which are insoluble in all menstrua.

2d. Change of Solvent Power by Evaporation.-Medicinal substances are very frequently deposited through a loss of the solvent power of the menstruum, in consequence of the evaporation of alcohol during percolation, or particularly so upon mixing the reserved alcoholic with the evaporated aqueous percolate.

*"Precipitates in Fluid Extracts," Proceed. Am. Phar. Assoc., 1882, p. 509; 1883, p. 336; 1884, p. 410; 1885, p. 411.

3d. Change of Temperature.-Through a lowering of the temperature, precipitation results from the inability of the liquid to hold in solution matter which was perfectly soluble in it at a higher temperature. For this reason many manufacturers prefer to prepare their fluid extracts during the winter.

"The fact that the drugs employed are merely air-dry and contain varying amounts of moisture, gives rise to the most important cause of precipitation, namely the change of the alcoholic strength of the menstruum. Some plant powders are very hygroscopic and absorb from 5 to 15 pounds of water per 100, absorbing moisture even in the driest weather. Hence when such drugs are percolated the first part of the percolate contains the water, which is thereby converted into a dilute alcohol, and hence differs from later percolates in alcoholic strength."

This is illustrated by Lloyd in Fluid Extract of Cannabis, which, upon percolation with alcohol, yields a first percolate of reddish-brown color, while the later ones are of deep green color. "The first portions of such percolates contain gum, extractives, and bodies which are more soluble in water than alcohol, while the last portions contain the resins, oils, and such bodies which are more soluble in an alcoholic menstruum; hence, when the several percolates are mixed, a gradual separation of the several dissolved matters takes place.'

Still another cause is given by Lloyd, as follows:

"The solvent power of the menstruum varies at different stages of the operation of percolation, aside from that due to the presence of more or less water. . . . Plants contain more or less of gums, gummy extractives, fixed and volatile oils, resins, oleoresins, resinoids, glucosides, tannates, glucose, sugar, chlorophyll, alkaloids, inorganic salts, etc. As the menstruum enters the powder it extracts the matter soluble in that fluid, and this at once forms a new menstruum, which has power to dissolve substances which are only partly soluble or insoluble in the original menstruum. Thus, during percolation, a constantly changing menstruum is passing through the powder, although the original menstruum be the same. The percolate is accordingly variable in composition and solvent powers; it may be considered as a collection of percolates and menstrua of different solvent power and varying composition, and hence one fraction of it may react with another, giving rise to precipitation."

The quality, that is, strength of a fluid extract or of any liquid pharmaceutical preparation should never be judged by its color. The amount of solid residue left upon evaporation, or the specific gravity, gives also no reliable criterion; the only sure method of ascertaining the medicinal value of such a preparation is to test its activity physiologically, or where it is possible, to make an assay of its active constituents.

CHAPTER XXIX.

SYRUPI (Syrups-Sirops-Sirupi).

SYRUPS are dense saccharine solutions, generally medicated or flavored.

A dense solution of sugar in water is called simple syrup. When this is impregnated with one or more medicinal substances, it is called a medicated syrup.

Simple syrup is employed as a vehicle for the administration. of medicinal substances. In order to render it more pleasant and better able to disguise the taste, syrup flavored with aromatic substances is also employed.

The presence of sugar exerts a strong preservative influence upon aqueous extracts of plants, which, without this, would ferment quickly. The preservative action of concentrated solutions of sugar is such, that they do not afford nourishment for micro-organisms, since the sugar withdraws water from these, which is essential to their cell-growth. For this reason, the amount of sugar in the syrup must be adjusted with a view to its preservation. Should the syrup be too concentrated, upon standing, a portion of the sugar is liable to crystallize out, causing thereby a diminution in saccharine strength, giving rise to the same difficulty of fermentation that would take place were the syrup made too weak. For the preparation of simple syrup, the U.S. Pharmacopoeia employs about 18.6 parts sugar to 10 parts of water,* the British Pharmacopoeia 20 parts to 10, the German Pharmacopoeia 15 parts to 10, the French Pharmacopoeia 18 parts to 10.+ If the solution contains alcohol or much extractive, then a correspondingly smaller amount of sugar must be taken. Only the best refined white sugar should be employed, and this should conform to the U. S. Pharmacopoeia requirements of purity.

PREPARATION. The method of preparation depends largely upon the nature of the substances employed.

+ Differences of climate partly warrant this difference of concentration.

The so-called rock-candy syrup should not be employed in preparing the official syrups.

1st. The sugar is dissolved in the medicated liquid by a moderate degree of heat (for instance, a water-bath).

2d. The sugar is dissolved in the fluid by a moderate degree of heat, and the solution then raised to the boiling point.

3d. The sugar is dissolved by agitation or by percolation with the cold, medicated solution.

4th. The sugar is added in the form of ready-prepared syrup to the concentrated medicated liquid.

The hot process (1st and 2d) is employed in preparing syrups from such solutions of drugs as are not injured by heat. The first method is adapted for preparing such syrups as those of orange or lemon, as the degree of heat is not sufficient to cause any injury to the preparation. The main objection to this process, however, is that it does not yield as clear and bright a syrup as process No. 2. In the preparation of syrups from drugs which are not injured by heat, the second process is preferable. In this the syrup is raised to the boiling point, whereby albuminous matters are coagulated, which are afterwards removed by straining. Syrups which require concentration should be boiled briskly, until they have become sufficiently dense; this may be ascertained by dipping a rod or spatula into the liquid, and noting the viscosity on cooling. The syrup, on cooling, should not form a pellicle or crust upon the surface, which would show that it has been concentrated too far. The object of rapid concentration is to avoid the browning of the syrup, which is caused by the prolonged application of heat. Saccharometers are often employed for this purpose; these enable the operator to control the concentration to a close degree of accuracy.

The cold process is best adapted for the preparation of such syrups as those of garlic, almond, orange flowers, etc., as these depend on the presence of sensitive volatile principles for their activity. The sugar is dissolved either by simple agitation or by percolation as directed in the U. S. Pharmacopoeia. Syrups prepared according to this method from aqueous extracts of drugs, are very liable to ferment, owing to the presence of albuminous and certain extractive matters. These can be removed only by boiling, which causes their coagulation and precipitation. With this end in view, the Pharmacopoeia employs an alcoholic menstruum to exhaust the drug, thus avoiding the extraction of inert matter, while the active principles are retained in solution. In the concentration of these alcoholic solutions, care should be taken that the evaporation be carried on at as low a temperature as possible.

The method of preparing syrups by the addition of fluid extracts to simple syrup, is not under all circumstances advisable. Syrups made in this way usually deposit a sediment in time. The presence of a small amount of alcohol thus added is liable to bring about acetic fermentation of the syrup.