FLUIDEXTRACTA. U. S. (Br.) USD 1926
FLUIDEXTRACTS
" Fluidextracts are concentrated liquid preparations of vegetable drugs, containing alcohol either as a solvent or as a preservative, and bearing- a uniform relation to the drugs used so that 1 cc. of the fluidextract closely represents the useful constituents of 1 Gm. of the air dried and powdered drug of standard quality." U.S.
Extracta Liquida, Br.; Fluid Extracts; Extraits liquides, Fr; Extracta fluida, P. G.; Fluidextrakte, Fluseige Extrakt, G .
The Latin title Extractum �� Fluidum formerly used for fluidextracts was dropped by the U. S. P. VIII because of the confusion which resulted from the necessary bringing together of the extracts and fluid extracts due to a strict alphabetical arrangement; the name "fluidex-tractum " is now used for " fluidextract" and the latter made one word.
Fluidextracts were first introduced into the U. S. P. of 1850. They are now perhaps the most important class of liquid preparations in use. Their distinctive character is the concentration of the active ingredients of medicinal substances into a small bulk, in the liquid form, a cubic centimeter of any one of them representing a gramme of the crude drug.
It has been repeatedly proposed to make 50 per cent, tinctures or half-strength fluidextracts, the main object being to secure more representative preparations when made on the small scale. Experiments by Sayre, Gregory, Patch, and others prove that half-strength
fluidextracts possess no advantages over those of official strength. (D. C., 1897, 119, 147.) Fluldextracts U. S. P. X.
"The fluidextracts of this Pharmacopoeia, with few exceptions, may be classified according to the menstruum used in the extraction of the drugs and the processes of manufacture employed. Several drugs require special manipulation to obtain satisfactory
fluidextracts, and for these appropriate formulas have been devised and are printed in full in the text.
In the preparation of fluidextracts by the appended type processes
A, B
, or
C
, the rate of percolation must be carefully controlled and, for the quantities directed in the formulas of the Pharmacopeia, the flow should not exceed ten drops per minute until the percolate to be reserved is collected, and twenty drops per minute thereafter. One thousand Gm. of powdered drug may frequently be exhausted by percolation with sufficient menstruum to yield 3000 cc. of percolate, but, in all eases the percolation should be continued until the drug is practically exhausted. Fluid-extracts should be kept in tightly-stoppered, amber-colored bottles, protected from sunlight and extremes of temperature. After keeping for one month, the clear portion should be decanted from any sediment, the remainder filtered, and the liquids thoroughly mixed before storing.
" The percentage of alcohol in fluidextracts made by type processes
A, B,
or
C,
is variable and always less than that in the menstruum employed, due, among other causes, to loss of alcohol by evaporation during manufacture, the presence of a variable proportion of water in the air-dried drug, and to the extraction from the drug of its soluble constituents, which also often, vary greatly in different lots of the same drug. The percentage of alcohol in the finished product can therefore only be ascertained by an actual determination." U. S. (See Alcohol Determination, Part III.)
"
Type Process A
. � This process is recommended for fluidextracts that are made with a menstruum of alcohol, or a mixture of alcohol and water, by the usual process of percolation. Moisten 1000 Gm. of the powdered drug directed with a sufficient quantity of the prescribed menstruum to render it evenly and distinctly damp and to so maintain it during maceration for six hours in a tightly-covered container.
Then pack it in a cylindrical percolator, and add enough of the menstruum to saturate the powder and leave a stratum above it. When the liquid begins to drop from the percolator, close the lower orifice, and, having closely covered the percolator, macerate for forty-eight hours. Then allow the percolation to proceed slowly, gradually adding more menstruum until the drug is exhausted.
Reserve the first 850 cc. of the percolate (unless otherwise specified in the formula), recover the alcohol from the remainder of the percolate, and concentrate the residue to a soft extract at a temperature not exceeding 60� C. Dissolve the extract in the reserved portion, mix thoroughly, and finally add a sufficient quantity of the menstruum to make the fluidextract measure 1000 cc., or the volume determined by calculation from the assay.
"
Type Process B.
� This process is recommended for fluidextracts in which glycerin or an acid is used in the extraction and two menstrua are successively employed. Moisten 1000 Gm. of the powdered drug directed with a sufficient quantity of the prescribed Menstruum I to render it evenly and distinctly damp and to so maintain it during maceration for six hours in a tightly-covered container. Then pack it in a cylindrical percolator, add the remainder of Menstruum I, and when this has just disappeared from the surface, gradually add Menstruum II, constantly maintaining a stratum of liquid above the drug. When the liquid begins to drop from the percolator, close the lower orifice, and, having closely covered the percolator, macerate for forty-eight hours, and then allow the percolation to proceed slowly, gradually adding Menstruum II until the drug is exhausted.
Reserve the first 850 cc. of the percolate (unless otherwise specified in the formula), recover the alcohol from the remainder of the percolate, and concentrate the residue to a soft extract at a temperature not exceeding 60� C. Dissolve the extract in the reserved portion, mix thoroughly, and finally add a sufficient quantity of Menstruum II to make the fluidextract measure 1000 ce. or the volume determined by calculation from the assay.
"
Type Process C
� Fractional or Divided Percolation.�This process is especially recommended for drugs containing volatile constituents or constituents which are injured by exposure to heat. This process may also be used as an alternative process in the formulas in which Type Process A is directed. Divide 1000 Gm. of the powdered drug directed into three portions of 500 Gm., 300 Gm., and 200 Gm., respectively. Moisten the first portion of, the drug (500 Gm.) with a sufficient quantity of the prescribed menstruum to render it evenly and distinctly damp and to so maintain it during maceration for six hours in a tightly-covered container.
Then pack it in a cylindrical percolator, and add enough of the menstruum to saturate the powder and leave a stratum above it. When the liquid begins to drop from the percolator, close the lower orifice, and, having closely covered the percolator, macerate for forty-eight hours, and then allow the percolation to proceed slowly, gradually adding more of the menstruum.
Reserve the first 200 cc. of percolate, and continue the process until the additional percolate measures 1500 ee., the latter being collected in successive portions of 300 cc. Moisten the second portion of the powdered drug (300 Gm.) with a sufficient quantity of
the percolate collected in the preceding operation, immediately after the reserved portion, to render it evenly and distinctly damp and to so maintain it during maceration for six hours in a tightly-covered container.
Then pack it in a cylindrical percolator, macerate, and percolate as directed for the first portion of the drug, using as menstruum the several portions of percolate from the preceding operation in the order in which they were collected, and, if this is insufficient, follow with more of the original menstruum. Reserve the first 300 cc. of percolate, and continue the process until the additional percolate measures 800 cc., the latter being collected in successive portions of 200
cc. each.
Moisten the third portion of the powdered drug (200 Gm.), with a sufficient quantity of the percolate collected in the preceding operation, immediately after the reserved portion, to render it evenly and distinctly damp and to so maintain it during maceration for six hours in a tightly-covered container. Then pack it in a cylindrical percolator, macerate, and percolate as before, using as menstruum the several portions of percolate from the preceding operation in the order in which they were collected, and, if this is insufficient, follow with more of the original menstruum.
Collect 500 cc. of percolate, and mix this with the two portions previously reserved to make 1000 cc. of finished fluidextract. When Type Process C is directed for fluidextracts which are adjusted by assay to a definite alkaloidal standard, collect only 420 cc. of percolate from the third portion of drug instead of the 500 cc. directed above. Mix this percolate with the two portions previously reserved, assay a portion of the mixture and adjust its volume by the addition of the menstruum directed so that each 100 cc. of finished fluidextract will contain the prescribed amount of alkaloid.
"
Type Process D
. � This process is recommended for those fluidextracts in which extraction is effected by infusion and percolation with boiling water, alcohol being added to the concentrated liquid as a preservative. To 1000 Gm. of the ground drug add 5000 ec. of boiling water, mix thoroughly, and allow it to macerate in a covered container in a warm place for two hours. Then transfer the moist drug to a tinned or enameled metallic percolator, and allow percolation to proceed, gradually adding boiling water until the drug is exhausted. Evaporate the percolate on a water bath or steam bath to the volume specified, and when cold add the alcohol directed, and mix thoroughly. Allow the product to stand for seven days in a stoppered container, then decant the clear liquid, filter the remainder, and wash the residue on the filter with sufficient of a mixture of alcohol and water in the proportion used to make the
fluidextract measure 1000 cc." U. S.
The precipitation experienced when the evaporated weak percolate was added to the reserved portion, is considerably diminished by causing the former to be evaporated to a soft extract. This precipitation, formerly noticed more particularly in alcoholic fluidextracts, was due to the greater volatility of the alcohol in the weak percolates, which, when evaporated, left the residue to a great extent aqueous; when this was added to the strongly alcoholic reserved portion, a precipitation of resinous, and
frequently of active matter, took place, which necessitated the storing of the fluidextract until precipitation ceased, and subsequent filtration.
This is not altogether avoided by evaporating to a soft extract, but the loss of activity through precipitation is thus greatly diminished. Fluid-extracts invariably deposit insoluble matter upon standing, and those made in warm weather, owing to the greater solvent powers of the menstrua (due to the elevated temperature) are found to deposit more freely than the same kind of fluidextracts if made in the winter time with menstrua correspondingly reduced in temperature.
The reason for the apparent stability of the fluidextracts furnished by the large scale manufacturer, is that sufficient reserve stock is kept on hand to permit this precipitation to take place before marketing the products.
In the earlier formulas for fluidextracts in the U. S. P. glycerin was used too lavishly in the menstrua and many of the preparations were loaded with inert extractive matter. Scoville (J. A. Ph. A., 1920, ix, 868) has completed a study of the function of glycerin in the menstrua of fluidextracts and tinctures and points out the fact that glycerin in some cases must be considered as a solvent, and in others as a stabilizer. In some cases, as in a few of the alkaloidal and astringent drugs, it is a distinct disadvantage, as it retards extraction.
A useful distillatory apparatus has been contrived by Joseph P. Remington for recovering alcohol from weak percolates, and for general pharmaceutical uses. (See Practice of Pharmacy.)
Fluidextracts are mostly prepared by percolation (see under Extracta) but in a few instances maceration yields satisfactory results.
Several methods have been suggested for preparing fluidextracts more economically. The use of acetic acid as a menstruum to replace alcohol or diluted alcohol has the merit of economy. (See Extracta, also A. J. P., 1899, 1, 67; Proc. Pennsylvania Pharm. Assoc., 1898, 116; Ph. Era, 1898, 796; Proc. Minnesota Pharm. Assoc., 1902, 103; West. Drug., 1903, 652.)
The most important modification is the plan of repercolation, as proposed by E. R. Squibb, for this class of preparations as well as the dry extracts.
This process consists in the successive application of the same percolating menstruum to fresh portions of the substances to be percolated. The result is that the same menstruum, acting re-peatedly on unexhausted portions of the substance, becomes concentrated to the greatest possible extent, so that much of the menstruum is saved, while subsequent -evaporation is avoided.
Repercolation
is officially permitted, by the U. S., as an alternative process, and is generally employed by wholesale manufacturers.
H. Biroth (Pharm., April, 1877) proposed the method which he termed " insuccation," for making non-alcoholic fluidextracts; the advantages claimed for it are simplicity and economy. Colaz prepared fluidextracts from fresh plants by bruising and crushing them, and placing the mass in a dialyzer suspended in 90 per cent, alcohol; when the dialysis is completed, the liquid is evaporated to free it from alcohol, the remaining aqueous liquid retaining the active constituents in the proportions in which they are found in the plant.
(Ph. Post, xxix, 271.) For other methods which have been suggested for economizing alcohol � most of which have been abandoned � see U. S. D., 20th ed., p. 482.
Assaying Fluidextracts.
� The U. S. gives assay processes for the fluidextracts of alka-loidal drugs; these differ but slightly from the process used for the corresponding drug; they will be found in the succeeding pages under their appropriate headings.
A new method of assay for alkaloidal fluid-extracts, especially adapted to the mydriatie leaf drugs in that the interfering chlorophyll is removed, making only one shaking out operation necessary, was proposed by La Wall (J. A. Ph. A., 1912, 29), as follows: Place 25 Gm. of sodium chloride in a 100 ec. graduated cylinder, with water sufficient to make 85 cc. Add 5 cc. of the fluidextract and 5 cc. of 10 per cent, ammonia water. Agitate well for 1 minute, then pour upon a dry filter and collect 50 cc. of clear filtrate, which can be shaken out as directed in the final shake out of the ordinary assay process, using the solvent directed for the particular drug which is being assayed. The method does not work with cinchona, guarana or other drags containing large amounts of alkaloids in the form of cinchotannates.
The keeping quality of fluidextracts, judged from the alkaloidal content of those which are assayable, has been greatly overestimated. Scoville (/. A. Ph. A., 1919, viii, 799) made an exhaustive study of the keeping qualities of about fifty fluidextracts and tinctures. He found that deterioration is largely due to the unstable nature of the alkaloids in many cases and to the precipitation of secondary constituents that also carry down alkaloids. In general, he says that any large amount of precipitation is accompanied by a loss of strength.
Hauss-mann (A. J. P., 1895, 291,) after examining a large number of commercial fluidextracts, finds great variation in the quality, due to deviation from pharmacopceial processes.
