Glycerinum (U. S. P.)—Glycerin.
FORMULA: C3H5(OH)3. MOLECULAR WEIGHT: 91.79.
"A liquid obtained by the decomposition of vegetable or animal fats or fixed oils, and containing not less than 5 per cent of absolute glycerin (C3H5[OH]3= 91.79)"—(U. S. P.).
SYNONYMS: Glycerina (U. S. P., 1870), Glycerine, Glycerol, Propenyl alcohol.
History and Preparation.—Glycerin was discovered, in 1779, by Scheele in the saponification products of olive oil by means of litharge, and later recognized by him as a common constituent of other oils and fats, and therefore named the "sweet principle of fats." Chevreul gave it the name glycerin, and cleared up the nature of its combination in the fats. Glycerin, or glycerol, as it is now preferably called to indicate its alcohol character, is a trihydric alcohol (C3H5[OH]3), containing the trivalent radical "glyceryl" (C3H5). It exists in oils and fats, combined with palmitic, stearic, and oleic acids in the form of glycerylesters of these acids (tripalmitin, tristearin, triolein; also see under Adeps). In some oils and fats it is combined partially with other acids—e. g., in butter—wherein 5 per cent of the total fat is glyceryl-tributyrate, or tributyrin; in cod-liver oil it is said to exist in part combined with acetic acid, as glyceryl triacetate, or triacetin, etc. Glycerin also exists in the yolk of eggs and the human brain in the form of phospho-glyceric acid. Pasteur's researches have also established its occurrence as a regular constituent among the products of fermentation (see Alcohol).
On a small scale glycerin may be obtained in the process which led to its discovery, viz., that of making lead plaster (see Emplastrum Plumbi). The late Mr. Robert Shoemaker prepared by this method probably the first Commercial glycerin in the United States, in 1848, at $4.00 a pound (Amer. Jour. Pharm., 1879, p. 289). The article became official in the U. S. P., in 1850.
Large quantities of glycerin are now obtained as a by-product in the manufacture of soaps and candles. This was formerly thrown away as useless. The principle involved is simply that of splitting the fat into its constituents (fatty acid and glycerin) by adding the elements of water (see Emplastrum Plumbi). The process of saponification is being carried out in several different ways: (1) With alkalies; the fatty acids thereby combine with alkali and form soap (see Sapo); the glycerin in diluted form is contained in the aqueous layer below the soap. (2) With milk of lime (old process of Campbell Morfit, see this Dispensatory, previous revision), or with milk of lime and water in closed vessels under a pressure of 10 atmospheres and a temperature of 172° C. (242.6° F.) (Milly's Autoclave Process, see Prof. S. P. Sadtler, Handbook of Indust. Org. Chem., 1895, p. 56). The glycerin water separates from the layer of lime soap and fatty acids; glycerin is obtained therefrom best by evaporation in vacuo. (3) With superheated steam ("aqueous saponification") and subsequent redistillation of the raw glycerin. This method was introduced, in 1855, by Messrs. Wilson and Paine, and marked a great step forward in the problem of obtaining a pure article. In saponifying the fats with superheated steam, the temperature must not exceed 300° C. (572° F.), or else decomposition products will be formed. Both the fatty acid and the glycerin distill over. In redistilling the raw glycerin by superheated steam, the liquid is heated to about 180° C. (356° F.), and the steam has a temperature of about 110° C. (230° F.). For details regarding the manufacture of glycerin, consult the various works on chemical technology.
Description.—Glycerin is officially described as follows; "A clear, colorless, liquid, of a thick, syrupy consistence, oily to the touch, odorless, very sweet and slightly warm to the taste. When exposed to the air, it slowly abstracts moisture. Specific gravity, not less than 1.260 at 15° C. (59° F.). Soluble, in all proportions, in water or alcohol, also soluble in a mixture of 3 parts of alcohol and 1 part of ether, but insoluble in ether, chloroform, carbon disulphide, benzin, benzol, and fixed or volatile oils. Glycerin is slowly volatilized from an aqueous solution, at or above 100° C. (212° F.), with the vapor of water. Heated by itself to a higher temperature, it yields acrid decomposition products, boils at a temperature at or above 165° C. (329° F.), and is finally entirely decomposed and dissipated"—(U. S. P.). The exceedingly irritating decomposition products are chiefly due to the formation of acrolein (allyl aldehyde, C2H3.CHO), which is also formed when fats are burned, or when glycerin is heated with strong sulphuric acid. Yet Prof. Trimble has demonstrated (Amer. Jour. Pharm., 1885, p. 275) the propriety of the use of the vapors of pure glycerin for inhalations, the details being as follows: When 50 grammes of pure glycerin were slowly heated in an open capsule, vaporization became abundant at 130° C. (266° F.). At 264° C. (497.2° F.), slight boiling was perceptible, but very little was left, and the dense vapors formed had a purely sweet taste, absolutely free from any irritating quality. Pure glycerin, when heated to 150° C. (302° F.) in an open crucible, can be ignited, and burns with a blue flame. Glycerin of only 90 per cent can be burned with the aid of a wick, like alcohol, in a spirit lamp. Absolute glycerin has the specific gravity of 1.266 at 15° C. (59° F.), and boils at 290° C. (554° F.), while 95 per cent glycerin has a specific gravity of 1.2596 and boils at 164° C. (327.2° F.) (Gerlach). At one time crystallized glycerin, from a Vienna manufacturer, was brought to London, requiring the knife and hammer to break it. It resembled rock-candy (sugar), being in white, octahedral crystals, with considerable refractive power, and, when melted, the liquid glycerin presented all its usual properties, but could not be again reduced to the crystalline condition. It seems that prolonged exposure to a temperature of 0° C. (32° F.) will bring about crystallization, and contact with a crystal already formed will promote this process. The crystals, while hard and gritty, are very hygroscopic. More recently, some specimens, after being melted, were found by Prof. Trimble to have a high specific gravity (1.2618) (see Wallace Procter, in Amer. Jour. Pharm., 1885, p. 273).
Glycerin dissolves many vegetable exudations and resinous substances. It does not dissolve sugar or gum, but readily mixes with syrups and mucilages. It is insoluble in fatty matter, and can only be incorporated with it mechanically, to effect which it is necessary that the fat should have a soft consistence, which may be imparted to it by combination with oil of sweet almonds, or some other fixed oil. Glycerin mixes with acetic acid; moistens bodies without rendering them greasy, does not become rancid, and is easily charged with the aroma of volatile oils.
The solubilities of certain substances in glycerin (Klever) as taken from Chemiker Kalender, 1897, are as follows: One hundred parts (by weight) of glycerin dissolve at 15.5° C. (60° F.):
|Ammonium carbonate||20||Potassium arsenate||50|
|Ammonium chloride||20||Potassium bromide||25|
|Arsenic trioxide||20||Potassium chlorate||3.5|
|Arsenic pentoxide||20||Potassium cyanide||32|
|Barium chloride||10||Quinine tartrate||0.25|
|Benzoic acid||10||Sodium arsenate||50|
|Boric acid||10||Sodium biborate||60|
|Calcium sulphide||6||Sodium carbonate||98|
|Cupric acetate||10||Strychnine nitrate||4|
|Cupric sulphate||30||Strychnine sulphate||22.50|
|Lead acetate||20||Tannic acid||50|
|Mercuric chloride (corr. subl.)||7.5||Tartar emetic||5.5|
|Morphine acetate||20||Zinc chloride||50|
|Morphine chloride||20||Zinc iodide||40|
|Oxalic acid||15||Zinc sulphate||35|
Glycerin dissolves the vegetable acids, aloes, some resinous substances, the deliquescent salts, the sulphates of potassium, sodium, and copper, the nitrates of potassium and silver, the alkaline chlorides, caustic potash, caustic soda, baryta, strontia, bromine, iodine, and even oxide of lead, and one-fifth part of arsenous acid. It dissolves about 1 per cent of its weight of calcium sulphate, and 2 per cent of chloride of lead. It dissolves the salts of morphine, sulphate of quinine, and, when triturated with these, or with the salts of strychnine, veratrine, brucine, and other vegetable alkaloids, forms a medicinal cerate very useful for frictions and embrocations. It also dissolves sulphides of potassium, of calcium, and of iodine, iodides of sulphur, of potassium, and of mercury, and some chlorides. It promotes the solution of borax in tincture of myrrh, no water being required; added to tincture of kino it retards gelatinization. The vegetable extracts are soluble in it, some of the solutions, as of extract of belladonna, forming useful external applications. Being possessed of strong antiseptic properties, it preserves animal and vegetable substances; meat has been immersed in glycerin for several months and preserved its freshness. It dissolves the carbonate of iron immediately on its formation, giving a deep-green solution. Like sugar it arrests the conversion of the ferrous into ferric salts, and has kept iodide of iron for years without change. It may be used in the preparation of spirits (essences) of cloves, cinnamon, etc., for syrups of phosphate of iron, bromide of iron, and iodide of quinine, for preserving fresh lemon juice, and for preserving the soft consistence of I masses and confections. Thus it is seen that the solvent powers of glycerin, both diluted and undiluted, are very extensive and important.
By oxidation with cold nitric acid, glycerin yields glyceric acid (CH2OH.CH.OH.COOH) and a variety of other acids. Potassium permanganate in alkaline solution produces oxalic acid. Upon the latter reaction is based a quantitative determination of glycerin by Benedict and Zsigmondy, a process also indicated by Wm. Fox and J. A. Wanklyn (see Amer. Jour. Pharm., 1886, p. 248). Another method for the quantitative determination of glycerin, by L. Legler and O. Hehner (Amer. Jour. Pharm., 1887, p. 464, from The Analyst, Jan. and Feb., 1887), is based on the fact that glycerin can be completely oxidized to carbonic acid and water by being heated with sulphuric acid and potassium bichromate. Sulphuric acid combines with glycerin to form an ester glycerylsulphuric acid (SO4H.C3H5[OH]2). Likewise glycerin combines with phosphoric acid to form a similarly constituted compound (PO4H2.C3H5[OH]2). Nitroglycerin is a highly explosive compound that is made by methods safe only on a manufacturing scale and in the hands of qualified men (see Spiritus Glonoini). Glycerin liberates from borax half its quantity of boric acid; thus if blue litmus solution is added to separate quantities of neutral glycerin and borax solution, when mixed, a red color results. W. R. Dunstan (Amer. Jour. Pharm., 1883, pp. 447-456) has shown that the red color turns blue upon warming, and reappears on cooling. Again, when adding glycerin to a mixture of molecular quantities of bicarbonate of sodium and borax, the boric acid liberated by the glycerin will expel with effervescence half of the carbonic acid in the bicarbonate, and monocarbonate will remain (with reference to this reaction, see also Mr. L. F. Kebler, Amer. Jour. Pharm., 1894, p. 428).
Glycerin is capable of undergoing fermentation under certain conditions. A. Fitz (1877) obtained, by the action of a certain class of fungi, called Schizomycetes, from glycerin diluted with twenty times its bulk of water, large quantities of normal butylalcohol. and normal butyric acid; also ethyl alcohol, capronic acid, hydrogen, and carbonic acid. Freund has also shown that trimethyleneglycol (C3H8O2) is one of the principal products formed. This substance has more recently been demonstrated by A. A. Noyes and W. H. Watkins (Amer. Jour. Pharm., 1895, p. 639), to occur as a troublesome by-product in the manufacture of glycerin from fats that have undergone spontaneous saponification and subsequent fermentation.
Tests and Uses.—For medicinal purposes, glycerin only should be used that has been purified by distillation; an impure glycerin when applied to wounds or ulcers is very apt to cause a burning sensation, and a papular eruption on the skin; when pure it is unirritating. Formerly its impurities were more numerous than now, owing to the imperfect method of its manufacture. The process of purifying glycerin by distillation has reduced the proportion of ash considerably, which in pure distilled glycerin does not exceed 0.2 per cent, while undistilled glycerin from soap lyes may have from 7 to 14 per cent of ash. Impurities liable to occur in glycerin are: water, volatile fatty acids (e.g., formic and butyric acids), added sugar or glucose, empyreumatic substances, oxalic acid, chlorides, sulphates of calcium, magnesium, and heavy metals, as iron, lead, zinc, etc. Siebold (1889) observed the presence of arsenic in glycerin (in one instance, 0.04 per cent), an impurity due to the employment, during manufacture, of sulphuric acid containing it. When present in glycerin, arsenic is exceedingly difficult to remove; it is claimed that agitating with recently precipitated ferric hydrate will remove this contamination (Amer. Jour. Pharm., 1890, p. 523). The presence of iron in glycerin, due, according to Haussmann (Amer. Jour. Pharm., 1895, p. 84) to its being kept in tinned iron cans, disturbs the color of pharmaceutical preparations in which glycerin is combined with tannin, or phenols, or salicylic acid. Another impurity occasionally occurring in commercial glycerin is the trimethyleneglucol before mentioned. Glycerin, beside answering to the official description given before, should conform to the following tests of the U. S. P.: "If a fused bead of borax, on a loop of platinum wire, be moistened with glycerin, and then held in the non-luminous flame, the latter will be transiently tinted deep green. An aqueous solution of glycerin is neutral to litmus paper. When a small portion of glycerin is heated to boiling in an open porcelain or platinum capsule, and then gently ignited, it should burn and vaporize so as to leave not more than a dark stain (absence of dextrin and sugar), which would leave a bulky, difficultly combustible, charred mass); and on full combustion no residue whatever should be left (absence of fixed impurities). If 5 Cc. of glycerin be mixed with 50 Cc. of water and 10 drops of hydrochloric acid in a small flask, and heated for half an hour on a boiling water-bath, then 10 Cc. of the hot liquid mixed with 2 Cc. of sodium hydrate T.S. and 1 Cc. of alkaline cupric tartrate V.S., no yellowish-red cloudiness or precipitate should appear within six hours (absence of sugars). On gently warming a mixture of equal volumes of glycerin and of concentrated sulphuric acid in a test-tube, the liquid should not acquire a dark color (absence of readily carbonizable impurities). On gradually heating 5 Cc. of glycerin with 3 Cc. of diluted sulphuric acid in a test-tube, short of boiling, no offensive or acidulous odor should be evolved (absence of fatty acids, etc.). No color, cloudiness or precipitate should appear when separate portions of its aqueous solution (1 in 10) are treated with hydrogen sulphide or ammonium sulphide T.S. (absence of metals), barium chloride T.S. (sulphuric acid), calcium chloride T.S. (oxalic acid), or ammonium oxalate T.S. (calcium salts). If a mixture of 2 Cc. of glycerin with 10 Cc. of water, contained in a perfectly clean, glass-stoppered cylinder, be heated for five minutes in a water-bath at a temperature of 60° to 65° C. (140° to 149° F.), then mixed with 10 drops of silver nitrate T.S., and the cylinder set aside, well stoppered, in diffused daylight, no change of transparency or color should occur in the mixture within five minutes (absence of chlorides, and limit of impurities having reducing properties)"—(U.S. P.). The presence of butyric acid may be detected, according to the British Pharmacopoeia (1898), by adding a mixture of equal volumes of alcohol (90 per cent) and diluted sulphuric acid, and gently heating, whereupon the pineapple odor of butyric ether is at once developed. As pure glycerin does not polarize transmitted light, the presence of sugar may be easily recognized also by optical methods. The British Pharmacopoeia (1898) fixes the limit of arsenic in glycerin by the following test: "2 Cc. diluted with 5 Cc. of a mixture of 1 part of hydrochloric acid and 7 parts of water, 1 Gm. of pure zinc being added, and the whole placed in a long test-tube, the mouth of which is covered by a piece of filter paper moistened with a drop or two of test solution of mercuric chloride, and dried, should not afford a yellow stain on the paper, even after 15 minutes (limit of arsenium)"—(Br. Ph., 1898). (Also see article on arsenic in glycerin, by A. C. Langmuir, Jour. Amer. Chem. Soc., 1899, p. 133.) The most extensive use of glycerin, in the industries and arts, is in the manufacture of nitroglycerin; large quantities are also used in the making of cosmetics, and for filling wet-process gas meters to prevent the containing fluid from freezing in winter and evaporating in summer. It is also employed as a food preservative, and for the treatment of wine, vinegar and beer (this process being called scheelizing), and in addition to its use in pharmacy and medicine, it is also employed for many practical purposes in the mechanical arts.
Action, Medical Uses, and Dosage.—Stimulant, antiseptic, laxative and demulcent. Pure glycerin abstracts water from the tissues, leaving them hard and irritated, and if of the skin liable to crack; impure glycerin, besides acting in the same manner, is more of an irritant on account of traces of sulphuric and nitric acids as well as certain organic acids, and other deleterious substances contained in it. In view of these facts only the purest glycerin should be used, and that should be mixed with a certain amount of water or rose-water before using. Glycerin may be used in prurigo, psoriasis, impetigo, lichen, lepra, pityriasis, herpes exedens, and some syphilitic and strumous affections. M. Fonssagrives considers its usefulness in parasitical cutaneous affections to be due to its antiseptic, antiputrid, and antiparasitical properties. Glycerin has been used in the place of cod-liver oil, to improve nutrition in convalescence from exhausting diseases, and in asthenic conditions generally. It is also used as a solvent of many alkaloids, extracts, salts, acids, etc., etc., especially for local application to inflamed, ulcerated or suppurating parts; also, as stated above, to several cutaneous maladies. Pure glycerin has been recommended for diabetic patients by Drs. Pavy and Abbot Smith, as a substitute for cane sugar, honey, molasses, etc., sweetening tea, coffee, various drinks, cakes, etc., with it. It is generally regarded as a non-nutritious substance at the present day, and has lost prestige as a food in phthisis and diabetes, and other exhausting diseases. It can not compare with cod-liver oil for this purpose, though there is some good evidence that it lessens, and in some instances checks, the excretion of sugar in saccharine diabetes. Large amounts of glycerin act not unlike alcohol, producing intoxication and the same gastric effects. From one-third to one-twelfth of glycerin may be added to washes or cataplasms, to render them soothing, and to keep the latter moist for some time. It acts as an emollient and soothing application, absorbing moisture from the air, and preventing the parts to which it is applied from becoming too dry.
A very small amount added to a few grains of borax and rose-water, furnishes one of the most elegant and efficient washes for chapped hands, face, lips, or nipples. A small quantity of glycerin added to pills or extracts, will preserve them from becoming hard and moldy. Vaccine virus may be preserved by mixing it with glycerin. It has been highly recommended for deafness in which there is a partial or total absence of ceruminous secretion, by protecting the tympanum, and gradually restoring the parts to their natural condition; it is likewise said to cause hearing in cases where the tympanum is thickened and indurated, or where it is in an unsound state or destroyed by ulceration; but in this last case it is not permanent; and when there is a hardness of the cerumen, and induration of the tympanum, it has proved successful. The plan is to moisten wool with the glycerin, pure or diluted with water, and pass it into the ear. In fact water and glycerin, or glycerin alone, are the best solvents for impacted and hardened cerumen, and by softening the mass with either, it may be readily removed by syringing carefully with warm water. An efficient lotion for dressing the parts after the removal of the impacted mass, is the following: Rx Colorless hydrastis (Lloyd's), ʒj; glycerin, gtt. xx; distillate of hamamelis, q. s. fl℥ss. Mix. Sig. Apply warm to the parts by means of cotton. The bland and unirritating character of pure glycerin, in the presence of a little water, its permanence when exposed to the atmosphere (except its absorption of moisture), and the completeness with which it shields the parts covered by it, render it susceptible of many important applications. Mr. J. H. Ecky has given a formula for the preparation of a glycerin ointment, especially useful for chapped hands, lips, excoriations of the skin, etc. It will also serve as a medium for applying powders, etc., to ulcers, cutaneous affections, or other difficulties, by combining them with it, in the desired proportions. The formula is as follows: Melt together spermaceti half an ounce, and white wax 1 drachm, with oil of almonds 2 fluid ounces, at a moderate heat; put these into a Wedgewood mortar, add glycerin 1 fluid ounce, and rub together until well mixed and cold. An excellent lotion for cracked hands, and especially for those who work in water, is the following: Rx Carbolic acid (liquefied by warmth), gtt. v; tincture of arnica, fl℥ss; glycerin, fl℥ss; rosewater (or water or distillate of hamamelis), q. s. fl℥vj. Mix. Sig. Wash the hands thoroughly with asepsin soap and warm water, rinse them, and apply the lotion while the hands are still wet.
A Glycerin Balsam for chapped lips and hands is made by melting together 1 ounce, each, of white wax and spermaceti, then stirring in half a pound of sweet almond oil and 2 ounces of glycerin, and when nearly cold, half a drachm of attar of roses. Mr. Wilson recommends glycerin as an injection into the bladder to dissolve calculous deposits, especially urea, and phosphate of calcium; also to be used as a substitute for syrups in preserving fruits; mixed with alcohol or pyroxylic spirit as an economical fuel for spirit-lamps; and as a remedy in diseases of the mucous membrane of the stomach. Dr. Wm. Bayes advises a solution of tannic acid in pure glycerin as a local application to local hemorrhages, by a sponge or brush, also to the vaginal, uterine, urethral, rectal, or nasal membranes, where a strong and non-irritant astringent lotion is desired. Glycerin dissolves nearly its own weight of tannic acid; the solution should be recently prepared and be kept in the dark, else it will decompose (see Glycerites). On account of its affinity for the water of the tissues, glycerin may be used as an astringent. It has thus been employed to dry and constringe wounds, lessening the tendency to the formation of pus, and a cotton pledget first dipped in hot water, squeezed, and saturated with glycerin, applied to fresh wounds, is said to cause union by first intention. Glycerin is an efficient astringent for leucorrhoea. Otorrhoea, ozoena, and other catarrhal discharges may be lessened by the local use of glycerin. Abscesses, boils, carbuncles, and local oedemas, as of the prepuce, may be treated with it. A mixture of glycerin and water is in common use to relieve dryness of the mouth induced by febrile and other states. Internally administered, glycerin is somewhat laxative, and cures of chronic constipation and hemorrhoids, both blind and bleeding, have been accredited to its use. When used by rectal injection, or by means of the glycerin suppository, it certainly is a very efficient remedy for habitual costiveness, provided the fecal mass be located in the rectum, and there is no lesion of the parts. If the parts be sound and the glycerin pure, no smarting or pain is likely to follow its use. It may be employed even with very young infants, and a few injections will generally break up the constipation habit. Occasionally irritation of the rectum has followed in infants, but such instances are rare, and probably due to an unhealthy condition of the rectum or to the use of an impure glycerin. The amount to be used is from ½ to 1 drachm. A small glass syringe may be employed. Added to washes and ointments for skin diseases, glycerin aids in allaying itching, when present. One of the best applications for tibial ulcerations is the following: Rx Glycerin, ʒj; carbolic acid (melted by warmth), gr. iij; aqua pura, q. s. Oj. Mix. Sig. Bathe the part two or three times a day, and keep the part wetted by laying upon it a cloth saturated with the solution.
Dr. Goddard has given a formula for a very adhesive glycerin paste, suitable for fixing paper labels to glass and other surfaces, and which keeps well; it is to dissolve 1 ounce of gum Arabic in 2 fluid ounces of boiling water, add 2 fluid drachms of glycerin, and strain if necessary. This forms a valuable paste for druggists, chemists, and others. A glycerin jelly is prepared by intimately mixing half a drachm of soft soap with 2 fluid drachms of pure honey, then gradually adding 5 ounces of clear olive oil, stirring without intermission until all the oil is taken up. Care must be taken not to add the oil too fast. Or it may be prepared by rubbing and mixing well together half an ounce of powdered gum Arabic, and 4 ounces of simple syrup, then add the yolks of 3 eggs, and when well mixed, add gradually 4 ounces of olive oil, and 2 ounces of glycerin, previously mixed together. The ordinary dose of glycerin is 1 drachm, though from 2 to 4 drachms night and morning may be used.
Related Preparation.—GLYCONES, prepared by Eli Lilly & Co., Indianapolis, Ind., are rectal suppositories containing 95 per cent of pure glycerin, covered with an easily removable coating which is impervious and unchangeable, preserving the suppositories in all climates. They are designed to overcome constipation, and quickly and easily produce rectal evacuation.