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Pilulae. Pills.

Preparations:

Pilules, Fr.; Pillen, G.; Pillole, It.; Pildoras, Sp.

These are globular masses of a size convenient for swallowing. They are well adapted for the administration of medicines which are unpleasant to the taste or smell, or insoluble in water, and which do not require to be given in large doses. Deliquescent substances should not be made into pills, and those which are efflorescent should be previously deprived of their water by crystallization. Care should be taken not to combine materials the mutual reaction of which may result in a change of physical conditions.

Some substances have a consistence which enables them to be made immediately into pills. Such are the softer extracts and certain gum-resins, and the addition of a little water to the former, and of a few drops of alcohol to the latter, will give them the requisite softness and plasticity, if previously wanting. Substances which are very soft, or in the liquid state, are formed into the pilular mass by incorporation with dry and inert powders, such as wheat flour, starch, and powdered gum arabic, or with crumb of bread. Powders must be mixed with soft, solid bodies, as extracts, confections, soap, etc., or with tenacious liquids, as syrup, molasses, honey, mucilage or glycerin and the last-mentioned substance has been especially recommended in connection with a little alcohol. Heavy metallic powders are most conveniently made into pills with the former; light vegetable powders with the latter. Mucilage is very often used, but pills made with it are apt when kept to become hard and of difficult solubility in the liquids of the stomach, and if metallic substances are mixed with it the mass does not work well. A mixture of syrup and powdered gum arabic is not subject to the same inconveniences, and is an excellent material for the formation of pills. Honey evaporated to about half its bulk has been highly recommended. Confection of rose and glucose are among the best excipients, when the pills are to be kept long. For the same purpose of keeping the pills soft, the addition of a small portion of some fixed oil or deliquescent salt has been recommended, but glycerin is still better. Glycerin incorporated with one-twenty-fifth of its weight of powdered tragacanth is said to cause pills to remain soluble for almost any length of time. The official mucilage of tragacanth is an excellent excipient. Martindale prepares a mass by heating together with constant stirring to 115.5° C. (240° F.) five parts by weight of glycerin and one of flour, or, when a very firm mass is required, equal parts of flour and glycerin. It has been objected that pills made with glycerin could not be handsomely gilded or silvered, the luster of the metal disappearing. This is true, however, only of very recent pills, or of those in which an excess of glycerin has been used. Many powders require only water. Such are all those which contain ingredients capable of forming an adhesive or viscid solution with the liquid. Care should always be taken that the substance added is not incompatible with the main constituents of the pill.

The materials should be accurately mixed together, and beaten in a mortar until formed into a perfectly uniform and plastic mass. This should be of such a consistence that the pills may preserve their form, without being so hard as to resist the solvent power of the gastric fluids. As pills frequently become very hard by time, it is often convenient to keep the mass in a state fit to be divided when wanted for use. This may be done by wrapping it in waxed paper, putting it in covered pots, and occasionally moistening it as it becomes dry, or, more effectually, by keeping it in glass or well glazed jars, accurately closed with rubber cloth. The mass is made into pills by rolling it with a spatula, or with a flat, smooth piece of hard wood, into a cylinder of precisely the same thickness throughout, and of a length corresponding to the number of pills required. It is then divided as equally as possible by the hand, or, more accurately, by a machine. (See Remington's Practice of Pharmacy, 5th edition, p. 1217.) The pills receive a spherical form by being rolled between the fingers or by the use of one of the pill rolling machines. Mialhe describes a little instrument for rolling pills, composed of two circular plates, one about 12 inches, the other 6, in diameter, the former having a ledge at the border one-third of an inch high, the latter with a similar ledge, varying, according to the size of the pills, from less than a line to nearly two lines, and with a strap on the back by which it can be fitted to the hand. This is to be moved in a rotary manner upon the larger plate, holding the divided portions of the pill mass. Similar pill rollers made of wood are now in use. In order to prevent the adhesion of pills to one another, or to the sides of the vessel in which they may be placed, it is customary to agitate them with some dry powder, which gives them an external coating, that serves also to conceal their taste. For this purpose magnesium carbonate, rice flour, or starch may be used. Magnesium carbonate is sometimes incompatible with one of the ingredients of the pills, and licorice root is then preferable, though it occasionally becomes mouldy with very damp pills. The powder of lycopodium, which has been long in use in Europe, is now considerably employed in this country, and is perhaps one of the best substances for the purpose. It is the custom in some sections of the United States, particularly on the Pacific coast, to give the pill a coating of gold or silver leaf. This is done by agitating the pills, prepared without dusting powder, and with their surface still damp, or coated with a very small quantity of mucilage, with gold or silver leaf, in a hollow spherical wooden box made by turning two hemispheres out of hard wood, fitting each other, and provided with a short handle.

It was proposed by Garot to cover pills with gelatin, which answers the purpose of concealing their taste and odor and counteracting deliquescence or chemical change from exposure to the air, but it sometimes interferes with their solubility in the stomach. This method of coating is largely used at the present time. One of the best machines that have been devised for gelatin coating pills extemporaneously on the small scale is that of H. Maynard, of Chicago. This consists of a circular plate in which are affixed twenty fine needles; the pills are rolled into depressions, and are easily impaled on the points of the needles; they are then dipped into a solution of gelatin, gently rotated, and allowed to cool. Another plan, less effectual, but more convenient, is to introduce the pills into a spherical box, to drop on them enough syrup simply to moisten their surface, then to give a rotary movement to the box until the pills are uniformly covered, and finally to add by degrees either powdered French chalk, elm bark, or some similar substance, shaking the box with each addition, and continuing the process until nothing more will adhere to the pills. The investing material may be rendered agreeable to the taste and smell by aromatic additions, if deemed advisable. Calloud found that a good powder for coating pills, because little disposed to attract moisture, is made by boiling one part of flaxseed and three parts of white sugar with sufficient Water until a thick mucilage is formed, evaporating this carefully to dryness, and then pulverizing. The same writer has since suggested, as still more effective, a powder made by forming a mucilage with one part of tragacanth and two parts of water, pressing this through linen, mixing it with twenty parts of sugar of milk, spreading the paste thus made in thin layers to dry, and then powdering. The pills may be simply moistened with water and then shaken in the powder. L'Hermite proposed first to agitate the pills in a mortar with a little concentrated solution of gum, and afterwards to put them into a box containing dry and very finely powdered sugar, to which a rotary motion is given. If the coating be not sufficiently thick, the process may be repeated. (J. P. C., xxv, 460.) For a list of excipients for pills by J. Cohn, see Proc. A. Ph. A., 1900, 469 from Ph. Ztg., 1900, 221; also G. Gugge, A. Ph. A. Year Book, 1914, p. 81.

Gelatin coating on the larger scale is accomplished by the use of the vacuum apparatus of J. B. Russell (see Remington's Practice of Pharmacy), or by simply rotating the pills in contact with a solution of gelatin in large spherical vessels, such as are used for sugar coating.

The sugar coating of pills is now conducted upon a large scale by manufacturers, who send immense quantities both of popular and of official pills into the market thus protected. The process employed is similar to that of the confectioners in coating almonds. After having been thoroughly dried, the pills are put into a hemispherical tinned copper basin, which is suspended from the ceiling and moved quickly backward and forward with an eccentric motion, so as to cause a constant attrition among the pills. First a little very thick syrup, or syrup of gum, is introduced in order to give a thin coating to their surface, and afterwards very finely powdered and very dry white sugar is sifted or thrown over them, the motion being constantly maintained. The sugar is fixed by the moist surface of the pills, and the coating made compact and smooth by the attrition. The process is aided by a gentle heat, but the heat must be guarded, lest the pills be much softened, and thus lose their shape and even discolor the coating. Dexterous manipulation is necessary in order that the process may succeed thoroughly. For practical remarks on the sugar coating of pills, see an essay by H. C. Archibald in A. J. P., 1867, p. 199, and by Wm. R. Warner, dr., and T. S. Wiegand in A. J. P., 1902, 32. On a larger scale a pill coater of copper of peculiar construction, heated by steam pipes, is now used.

Still another method of coating pills, proposed by E. K. Durden is to cover the pills with collodion, which completely conceals the taste. The solution employed by Durden had the sp. gr. 0.810, and two dippings gave a sufficient coating. (A. J. P., xxi, 183.) It is, however, yet to be. determined whether a coating of collodion would yield readily to the solvent powers of the gastric juice. Blanchard covers pills with a solution of Tolu balsam in ether, but H. C. Baildon objects to this, that it takes too long to dry, and suggests as a substitute a solution of a drachm of the balsam in three drachms of chloroform, which dries sufficiently in twenty minutes. If old and solid Tolu balsam be selected, it will be less liable to the objection of drying slowly. This balsam is officially employed in coating the U. S. pills of ferrous iodide. A solution of mastic in ether has also been used for coating pills, and the white of egg has been recommended for the same purpose.

Pills are sometimes coated with substances which do not dissolve in the stomach, with the object of permitting the passage of the undissolved pill into the intestines; for this purpose keratin coating has been largely used. (See Keratin, Part II, and Remington's Practice of Pharmacy, sixth edition.) Salol has also been employed, by melting it in an enamelled pan at a temperature of about 50° C. (122° F.) and dropping in the pills, rotating until covered, and then transferring to a dry pan, still rotating (to prevent adhesion) until cold.

An improved (method of salol coating for pills intended for enteric use has been contributed by J. C. and B. L. DeG. Peacock (Proc. P. Ph. A., 1915, p. 258). The particular points to be observed are the amount of salol to be used and the shape and size of the vessel used in melting the salol.

W. Q. Toplis (Proc. P. Ph. A., 1915, p. 262) proposes stearic acid as an enteric coating for pills and gives details of the method to be followed in producing a satisfactory article.

Pills which are to be kept long should be well dried, and put into bottles with loosely fitting stoppers to prevent mouldiness. Though the U. S. Pharmacopoeia, in almost every instance, orders the mass to be divided into pills, yet it should be understood rather as indicating the number of pills to be made from a certain quantity of the mass, -when particular directions are not given by the physician, than as requiring the division to be made immediately after the materials have been mixed. It will be found convenient by the apothecary to retain a portion of the mass undivided, especially when it is desirable to keep the pills soft. The British Pharmacopoeia furnishes formulas for pill masses, using the title of "Pilula" instead of "Massa," the title of the class adopted by the U. S. Pharmacopoeia; there is, in our opinion, a decided advantage in selecting a name for the class which is not likely to be confused with that used for the divided pills.

Pills containing silver nitrate, potassium permanganate or other easily oxidizable substances, should be made by diluting with kaolin or talc and massing with petrolatum or mixtures of petrolatum and paraffin. All organic matter should be excluded.

Compressed pills are made directly from the medicinal substance without the aid of an excipient. The drug, if not already in granular powder, is made so, and then forced into pill shape by means of a powerful press. For certain substances which are crystalline in structure, such as quinine bisulphate, potassium bromide, and potassium iodide, and which have some cohesiveness and yet are of easy solubility, the process is a good one. An apparatus was contrived by J. P. Remington for compressing pills (see 16th ed., U. S. D., and Practice of Pharmacy, 5th ed., page 1233). It is made of cast steel; the base has two counter-sunk depressions with a short post in the center of each, and a lenticular depression is made in the upper surface of each post. A steel cylinder having a central aperture of the diameter of the post is placed in the depression, the proper quantity of powder is introduced, and the plunger, which has a corresponding lenticular depression on its lower surface, is placed on the powder and is struck a quick blow with a mallet; the powder is compressed, and the pill adheres to the cylinder; by removing the cylinder and holding it over a box and tapping the plunger again lightly, the pill is forced out and falls into a box.

Compressed tablets, are now used to an enormous extent, being made by various manufacturers with machinery of ingenious construction; the fact of their requiring no excipient, the ease with which they can be tested, and their permanent character (in most cases being just as valuable years after they were made as when fresh) have caused their extensive employment. Care should be taken, however, not to use them in those few cases where very prompt action is required, as the powerful compression to which they are subjected renders them less quickly effective than the same drug administered in the form of a loose powder.

For a description of some of the more important forms of pill compressing machines with illustrations, see Remington's Practice of Pharmacy, sixth edition.


The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.



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