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Indica the active resin would be thrown out of solution, and floating on top might cause serious symptoms; but in many other instances the precipitate would be inert and filtration would be in order. Water is the solvent for albuminous, gelatinous, gummy, and saccharine bodies and for a large number of inorganic salts; while Alcohol is the solvent for volatile oil and resins, gum-resins, resinoids, balsams, and all drugs containing these as their active principles. The solvent power of either Alcohol or Water for their particular substances decreases in proportion to the amount of the other added.
Instances of Pharmaceutical Incompatibility. Resinous tinctures of Fluid Extracts with aqueous solutions.
Tincture of Guaiac with spirit of nitric ether.
Compound Infusion of Gentian with infusion of wild cherry.
Therapeutical Incompatibility arises when two agents are administered together which oppose each other in their action on the human system,―as for instance Belladonna in any form with Physostigma. But in many cases physiological antagonists are designedly prescribed together, one as a guard against the action of the other, as in the hypodermic administration of Morphine guarded by Atropine. The antagonists to each of the active medicinal agents may be found in the section on Materia Medica under their various titles; but they may be well summarized as to the most important ones in the following list.
Aconitine,-Atropine, Digitalin, Strychnine.
Ammonium Chloride,-Chloral hydrate.
Atropine,-*Aconitine, *Bromal-hydrate, Chloral-hydrate, Hydrocyanic Acid, Jaborandi, Muscarine, *Morphine, Physostigmine, Phytolacca, Pilocarpine, Quinine. [Those marked will not prevent death from a lethal dose of Atropine, though the latter will prevent death from a lethal dose of either of them.]
Barium,-Sodium Sulphate, Potassium salts.
Calabarine, -Chloral hydrate.
Chloral hydrate,-Ammonium Chloride, Atropine, Brucine, Calabarine, Carbolic Acid, Codeine, Physostigma, Picrotoxine, Strychnine, Thebaine.
Digitalin,-Aconite, Muscarine, Saponin.
Morphine,-Atropine, Caffeine, Chloroform, Cocaine, Daturine, Hyoscyamine, Nicotine,
Opium,-Atropine, Gelsemium, Veratrum Viride.
Strychnine,-Alcohol, Chloral, Hydrocyanic Acid, Nicotine, Nitrite of Amyl.
The Dangers of Incompatibility may in a great measure be avoided by the use of the utmost simplicity in prescribing. The subject can only be glanced at within these pages, but the following simple rules may help the burdened memory of the student and the practitioner.
(1). Never use more than one remedy at a time, if one will serve the purpose.
(2). Never use Strong Mineral Acids with other agents, unless you know exactly what reaction will ensue. They decompose salts of the weaker acids, and form ethers when combined with alcohol. Never combine free acids with hydrates or carbonates.
(3). Select the simplest solvent, diluent or excipient you know of, remembering that the solvent power of alcohol and of water for their respective substances decreases in proportion to the quantity of the other added.
(4). Generally do not combine two or more soluble salts; for such salts in solution, when brought together, usually exchange their radicles, thereby forming an insoluble compound.
The following more or less insoluble salts will be formed whenever the materials of which they are composed are brought together in solutions: the Hydrates, Carbonates, Phosphates, Borates, Arseniates and Tannates of most earthy and heavy metals and alkaloids, and the metallic Sulphides; the Sulphates of Calcium, of Lead, and the subsalts of Mercury; the Chlorides, Iodides, and Bromides of Bismuth, Silver, Lead, and Mercury; the Iodides of Quinine, Morphine and most alkaloids.
(5). Never order a drug in combination with any of its Tests or Antidotes.
(6). Never prescribe a Glucoside, (as Santonin, Colocynthin, etc.), in combination with free acids or with a substance containing Emulsin, as these agents will decompose it.
(7). Aconite should be ordered in water alone, Mercuric Chloride by itself in water or in simple syrup. The latter drug is incompatible with almost everything, even the Compound Syrup of Sarsaparilla being said to decompose it.
(8). Iodide of Potassium decomposes most of the metallic salts, and is one of the drugs which are best administered alone.
(9). The following named substances are incompatible with so many others that it is best to always prescribe them alone; they are best given in simple solution:
Dilute Hydrocyanic Acid.
Mercuric Chloride (Corr. Sub.).
Syrup of the Iodide of Iron.
Tinct. Ferri Chloridi.
Citrate of Iron and Quinine.
Tannic and Gallic Acids.
(10). Silver Nitrate and the Acetate and Sub-acetate of Lead, though incompatible with almost everything, may be combined with Opium, the latter forming with Opium a compound, which, though insoluble, is therapeutically active as an astringent and anodyne lotion. Silver Nitrate with Creasote forms an explosive compound.
(11). Tannic and Gallic Acids, and substances containing them (as the Astringent Bitters), precipitate albumen, alkaloids and most soluble metallic salts. They may be prescribed with the proto-salts of Iron, but not with its per-salts. Calumba is the best vegetable tonic to use with ferric salts, as it contains neither tannic nor gallic acids. Tannic Acid precipitates gelatin.
(12). Iodine and the soluble Iodides are incompatible with the alkaloids and substances containing them, also with most metallic salts.
(13). Alkalies neutralize free acids, and precipitate the alkaloids and the soluble non-alkaline metallic salts. Oxides of the Alkalies decompose salts of the metals proper, and salts of the alkaloids, precipitating their bases; but the base may be soluble in an excess of the alkali.
(14). Resinous Tinctures or Fluid Extracts, (e. g., Tinct. Cannabis Indica) when combined with aqueous solutions, should always have Acacia or some other emulsifying agent added, to prevent the separation of the resin, which otherwise will be deposited on the sides of the bottle or will float on top of the mixture.
(15). Tincture of Digitalis should not be mixed with aqueous or syrupy solutions, for in such cases a decomposition of the active principles may occur, forming new and poisonous ones.
LIQUID EXTEMPORANEOUS PREPARATIONS.
Mixtures (Mistura),-in official pharmacy are aqueous preparations containing some insoluble ingredients held in suspension by an appropriate vehicle. In extemporaneous pharmacy, however, the term Mixture is applied to every fluid compound intended for internal use, except a few which bear distinctive titles, such as Emulsions, Draughts, Enemas, Elixirs and Drinks. The simplest form of mixture in this extended sense is that
in which two or more liquids are mixed together; but a great variety of substances may be prescribed in this form, chief among which are most of the soluble salts, light insoluble powders, salts which may be diffused by agitation, extracts, gum-resins, and the fixed essential oils. They are generally ordered in 2, 3, 4, 6, 8, 10 and 12-ounce vials.
The substances suitable to the mixture-form, properly so called, are those which, though more or less insoluble in water, will mix with it by agitation, trituration, etc. Those most frequently ordered follows:
Diffusion by Agitation :—
Calcii Phosphas Præcip.
Suspendible by Viscid Excipients :—
Ferri Carbonas Saccharatus.
Best suspended by the aid of a fixed oil or yolk of egg:-
Ext. Cannabis Indicæ.
Miscible only by Trituration :
Antimonii et Potassii Tartras.
Solutions intended for internal administration are classed as Mixtures in extemporaneous pharmacy, for the reason stated above. The following list of acids and salts comprises most of the solids which are best adapted for use in liquid form, by reason of their solubility in water.
Ferri et Animonii Citras.
Potassii et Sodii Tartras.
A few require the use of viscid substances as vehicles or correctives. They are as follows:
Certain salts are best ordered by prescribing such agents as will when in solution together react upon each other and produce the desired salt. Instances of this may be found in the pharmacopoeial processes for most of the official Liquores; the salts so produced being the following:
Arsenii et Hydrargyri Iodidum.
Certain other substances require the addition of other agents in order to form eligible solutions. Such are the following:
Quinine Sulphas,-requires acidulated water for its solution, the acid used being generally Sulphuric diluted, or the Aromatic Sulphuric. This method of prescribing this salt develops its bitter taste to the utmost, and is often avoided by ordering the drug to be suspended in a viscid liquid, such as Pulv. Acacia in Syrup of Ginger. In such a case an officious dispenser anxious to show his smartness may add some dilute Sulphuric Acid to dissolve the Quinine and thus defeat the object of the prescriber.
Sulphate of Quinine may be prescribed with Aromatic Spirit of Ammonia, Spirit of Nitrous Ether, Tinctures or other alcoholic preparations together with Glycerin or Syrup and Water. In such cases the salt should be first dissolved in the alcoholic portion of the prescription; then the glycerin or syrup, and finally the aqueous portions should be added gradually. It may also be ordered with dilute Sulphuric Acid and some vegetable infusion containing Tannin, in which case a precipitate of Tannate of Quinine will be produced. This of course should not be filtered, but should be dispensed with a "Shake-label."
[For the use of " Veloutine" as a vehicle for the use of Quinine Salts, see ante, pages 187, 213.]
Chinoidin, Cinchonine Sulphate and Quinidine Sulphate,-also require the addition of dilute mineral acid for their solution in aqueous mixtures.
Iodine, requires the addition of Iodide of Potassium for its solution in a convenient quantity of water, as in the case of the official Liquor Iodi Compositus.
Red Iodide of Mercury,-requires the addition of Iodide of Potassium or Mercuric Chloride for its aqueous solution.
Potassii Bitartras, Cream of Tartar,-requires the addition of Borax or Boric Acid for its solution in water.
Medicated Waters (Aqua).
Benzoic Acid, -requires the addition of Borax to aid its solubility in water, an equal part of the latter making it 5 times more soluble than when alone.
Lime, is more soluble in sweetened water than in plain water, the sugar aiding its solution.
EXCIPIENTS are substances which give form and consistence to prescriptions, and serve as vehicles for the exhibition of the other ingredients. Some of the excipients are diluents, or agents which effect the dilution or division of the active ingredients; while others act in the double capacity of diluents and flavoring agents. The excipients most generally used in mixtures may be tabulated as follows, viz. :—