History.—Suppositories are globular, conical, cylindrical, or club-shaped solid bodies designed for introduction into the urethra, rectum, or vagina, in order to effect a therapeutical influence upon the adjacent parts or upon the general system. In a few instances they are prepared of articles not readily liquefying at the animal temperature, but, generally, they should be slowly fusible. The quantity of the active medicinal agent in each suppository, should, as a general rule, be about 3 times its dose for internal administration; however, with certain articles, or for certain results, more or less of this quantity will occasionally be required, according to the circumstances. Heretofore, when suppositories have been ordered by the physician, they were prepared by pouring the partially cooled mass, of which they were composed, into paper cones, the paper not being removed until the suppository became thoroughly hardened. The only advantage this method possesses is the readiness with which the cones may be made, and of any size required. The objections to it are the length of time required to finish the suppository, and the uncertainty of having the external surface clear, regular, and polished. In the preparation of suppositories, two things are especially required: (1) A composition which will permit the active ingredients to be so regularly diffused that each suppository will contain an equal quantity of the medicinal agent; the composition when cold must be firm, smooth, not liable to crack or split, must not adhere to the mold, and must be readily fusible at the temperature of the body. (2) A mold which, with as little extra manipulation as possible, will give smooth suppositories, of uniform size, shape, and weight, which will permit of their being made with as little loss of time as possible, and from which the suppository can be promptly removed.
For the first purpose, cacao butter (Oleum Theobromatis) is generally preferred by pharmacists, being used alone, especially when employed in cold seasons; or, in warm seasons, with the addition of 1/5 or 1/8 of wax or spermaceti. Spermaceti is usually preferred to wax, on account of its congealing with greater rapidity. Bullock and Crenshaw preferred, during warm weather, the addition of from 1/16 to the 1/20 of paraffin. Dr. W. B. Chapman, of Cincinnati, who at one time made a specialty of suppositories, preferred 1/8 of Japan wax. The amount of these articles to be added, will depend entirely upon the season and the temperature, as well as upon the latitude; thus, in summer, more of the hardening body will be required. The quantity will necessarily have to be determined by experiment, in different latitudes. In this latitude 1/4 of spermaceti is added during the hot summer months, and 1/6 during the winter; or 1/8 of Japan wax in winter, and 1/6 or 1/4 in summer. Curd soap was directed in some formulae of the British Pharmacopoeia, 1885. But it must be remembered that there are certain medicinal agents that contribute to the hardening of the cacao butter, as, most dry vegetable or mineral powders, especially iodides of lead and of cadmium, carbonate of lead, oxide of zinc, etc., in which instances no hardening aid is required. On the other hand creosote, chloral hydrate, camphor, carbolic acid, and the essential oils modify the consistence of cacao butter so that together they liquefy at a heat lower than the ordinary fusing point of the butter.
Various instruments have been proposed for making suppositories, and the reader is referred to Amer. Jour. Pharm., 1852, p. 211; 1861, pp. 5 and 202; 1867, p. 121; 1868, pp. 52 and 223; 1869, p. 59; to Proc. Amer. Pharm. Assoc., 1865, p. 65; 1866, p. 155; 1867, p. 167; 1868, p. 111; and to Caspari’s, Coblentz’s and other well-known works on pharmacy. Three sizes are to be preferred, two for the rectum, of 15 or 20 grains, each, for children, the other of 30 or 40 grains, each, for adults; likewise, one for the vagina, of about 120 grains, each. The weight of the suppositories will, of course, depend upon that of the medicinal agent added to the cacao butter—hence, there will always be a variation in weight of a few grains in the different kinds of suppositories. The ordinary weight of the U. S. P. and Br. Pharm. is 15 grains. Three varieties of molds have been used: (1) Individual hard-metal, cone-shaped molds; (2) separable solid blocks, hinged or otherwise, having several depressions, so that when apposed they form molds; (3) compression molds, for forming suppositories without the intervention of heat.
Upon the suggestion of Mr. H. S. Wellcome, of London, suppositories are now largely made of which the end to be inserted is formed largest—that is, tapering—bulb-shaped. This insures its retention by the sphincter muscles, much trouble having sometimes been experienced in retaining the ordinary conical suppository. When suppositories are prepared in advance by the pharmacist, they should always be kept in a cool place, and when passed over the counter, the person who receives them should be cautioned against placing the box or bottle containing them in the pocket, or in or near any place of too high a temperature; directions should likewise be given to keep them in a cool place until they are wanted for use, and then to handle them quickly.
Suppositories which contain a cavity from the base to a point near the apex, into which the active ingredient is placed, and the aperture then closed at base, have been recommended by some parties, but such are entirely unfit for use, as the medicinal substance, not being equally diffused throughout, instead of acting gradually and for a length of time, does not act at all until the material of which the suppository is made becomes liquefied, and then it acts suddenly and powerfully, perhaps irritating the parts to a considerable extent, and effecting more injury than benefit.
Preparation.—Dr. Chapman’s process is as follows: (1) Melt the cacao butter and Japan wax together, and then thoroughly incorporate the medicinal articles with it, either by rubbing them together in a mortar, or by first triturating the medicinal extract, powder, or tincture, etc., with part of the melted butter upon a warm slab, adding, if necessary, as little as possible of alcohol, oil, glycerin, or water, etc., sufficient quantity to aid in obtaining a thorough incorporation of the materials; and, when well incorporated, triturate this with the remainder of the melted liquid in a, mortar; continuing the trituration until the mass becomes quite thick, not, however, so thick as to prevent it from flowing readily into the molds. (2) The metallic block, before the melted mass is poured into the molds, must previously be set upon a lump of ice, and rest there until it has reached the dew point, as manifested by the thin layer of moisture upon its external surface (sometimes called sweating), then, and not till then, the mixture must be poured into the molds, as cool as may be without interfering with its flowing, and allowed to remain in until all the suppositories are hard and movable in the molds. (3) When the suppositories are sufficiently congealed, which require 2 or 3 minutes, very seldom exceeding 5, pressure with the ball of the thumb upon each suppository, will cause it to move in the mold, at the same time imparting a snapping or cracking sensation; then the block may be turned upside down, and the suppositories will fall out. If the suppositories are allowed to remain in the mold for too long a time, they are liable to split or crack.
The following method is that directed by the U.S. P.: “Take of the medicinal ingredient, the prescribed quantity; oil of theobroma, a sufficient quantity. Having weighed out the medicinal ingredient or ingredients, and the quantity of oil of theobroma required, according to the kind of suppository to be prepare (see below), mix the medicinal portion (previously brought to a proper consistence, if necessary) with a small quantity of the oil of theobroma, by rubbing them together, and add the mixture to the remainder of the oil of theobroma previously melted and cooled to the temperature of 35° C. (95° F.). Then mix thoroughly, without applying more heat, and immediately pour the mixture into suitable molds. The molds must be kept cold by being placed on ice, or by immersion in ice-cold water, before the melted mass is poured in. In the absence of suitable molds, suppositories may be formed by allowing the mixture, prepare as above, to cool, care being taken to keep the ingredients well mixed, and dividing the mass into parts, of a definite weight each, of the proper shape. Unless otherwise specified, suppositories should have the following weights and shape corresponding to their several uses: Rectal suppositories should be cone-shaped and of a weight of about one gramme (1 Gm.) [15.5 grs.]. Urethral suppositories should be pencil-shaped, and of a weight of about one gramme (1 Gm.) [15.5 grs.]. Vaginal suppositories should be globular, and of a weight of about three grammes (3 Gm.) [about 46 grs.]”—(U. S. P.). A cold process has been followed in which the ingredients, finely divided, are mixed in a mortar or on a slab, and compressed by hand, spatula, or other compressing instrument.
Formulas.—The following suppositories were official in the U.S. P., 1870:
Suppositoria Medicinal Ingredients Mix first with Cacao Butter Subsequently mix with Cacao Butter
ACIDI CARBOLICI Carbolic acid, grains xij Grains lx Grains cviii
ACIDI TANNICI Tannin, grains lx Grains lx Grains lx
ALOES Purified aloes (powdered), grains lx Grains lx Grains lx
ASAFOETIDAE Tincture asafetida, 1 fluid ounce; spontaneously evaporated Grains lx Grains lxxx
BELLADONNAE Alcoholic extract of belladonna, grains vj; water, q. s. Grains lx Grains cxiv
MORPHIAE Morphine sulphate, grains vj Grains lx Grains cxiv
OPII Extract of opium, grains xij; water, q. s. Grains lx Grains cviij
PLUMBI Acetate of lead, grains xxxvj Grains lx Grains lxxxiv
PLUMBI ET OPII Acetate of lead, grains xxxvj; extract of opium, grains vj; water, q. s. Grains lx Grains lxxx
Make of each formula twelve (12) suppositories. The following was official in the British Pharmacopoeia, 1885:
SUPPOSITORIA HYDRARGYRI (Mercurial suppositories).—Mercurial ointment, 60 grains; oil of theobroma, 120 grains. Mix with sufficient heat, and make into 15-grain suppositories. Each suppository contains 5 grains of ointment of mercury.
The following suppositories are official in the British Pharmacopoeia, 1898:
SUPPOSITORIA ACIDI CARBOLICI (Phenol suppositories).—Each containing 1 grain of phenol.
SUPPOSITORIA ACIDI TANNICI (Tannic acid suppositories).—Each containing 3 grains of tannic acid.
SUPPOSITORIA BELLADONNAE (Belladonna suppositories).—Each containing approximately 1/60 grain (0.001 gramme) of the alkaloids of belladonna root.
SUPPOSITORIA GLYCERINI (Glycerin suppositories).—Each containing 70 per cent of glycerin.
SUPPOSITORIA IODOFORMI (Iodoform suppositories).—Each containing 3 grains (0.2 gramme) of iodoform.
SUPPOSITORIA MORPHINAE (Morphine suppositories).—Each containing 1/4 grain (0.017 gramme) of morphine hydrochloride.
SUPPOSITORIA PLUMBI COMPOSITA (Compound lead suppositories).—Each containing 3 grains (0.2 gramme) of lead acetate, and 1 grain (0.067 gramme) of opium.