pharmaceutical incompatibility occurs as a result of mixing of two or more antagonistic substances and an undesirable product is formed which may

affect the safety, efficacy and appearance of pharmaceutical preparation. Pharmaceutical incompatibility may occur not only during compounding and dispensing but also at any stage during compounding and dispensing but also at any stage during formulation, manufacturing, packing or administration of drugs. TYPE OF INCOMPATIBILITIES: A) Physical incompatibility B) Chemical incompatibility C) Therapeutic incompatibility A)PHYSICAL INCOMPATIBILITY: When two or more than two substances are combined together, physical changes take place and an unacceptable product is formed. These changes which occurs as a result of physical incompatibility are usually visible and can be easily corrected by applying the pharmaceutical skill obtain a product of uniform dosage, substance to help in compounding of the prescription. An attractive incompatibilities’ may be corrected by using any one or more of the following method. •Change the order or mixing of the prescription •Emulsification •Adding of suspending agent •Change in the form of ingredients By adding, substitution or omission of therapeutically inactive Examples of physical incompatibilities

25gm Menthol 0. Hence ephedrine sulphate is substituted with anhydrous ephedrine to make a clear solution. In this prescription castor oil is immiscible with water . Example: 1 Ephedrine sulphate 0.To overcome this incompatibility an emulsifying agent is used to make a good emulsion INSOLUBILITY Insolubility means the inability of material to dissolve in a particular system. but anhydrous ephedrine is soluble in it. Example: 2 .vIMMISCIBILITY vINSOLUBILITY vPRECIPITATION vLIQUEFACTION IMMISCIBILITY Oils and water immiscible with each other. Example: Castor oil 15ml Water 60ml Make on emulsion.02ml Liquid paraffin (sufficient to make) 30ml The ephedrine sulphate is an alkaloidal salt and is not soluble in liquid paraffin. The major of incompatibilities are due to insolubility of the inorganic as well as organic compounds in a particular solvent. They can be made miscible with water by emulsification.

This type of substance create problem when they are dispensed in powder form. This occurs due to the lowering of the melting point of mixture to below room temperature and liberation of water of hydration. When the tincture containing resins is added in water. Example: The resins are insoluble in water. resin agglomerates forming indiffusible precipitates. Compound powder of tragacanth or mucilage of tragacanth is used as a suspending agent to make a suitable suspension PRECIPITATION A drug in solution may be precipitated. chloral hydrate and aspirin. Many chemicals form hydrates. The medicaments showing this type of behavior are camphor. menthol.Phenacetin 3g Caffeine 1g Orange syrup 12 ml Water up to 90ml In this prescription Phenacetin is an indiffusible substance. thymol. compounds with water of hydration. . phenol. a liquid or soft mass known as“eutectic mixture” is produced. This can be prevented by slowly adding the undiluted tincture with vigorous stirring to the diluted suspension Or By adding some suitable thickening agent LIQUEFACTION When certain low melting point solids are mixed together. if the solvent in which it is insoluble is added to the solution.

2) Adjusted: In adjusted incompatibilities the chemical interaction can be prevented by addition or substitution of one of the reacting ingredients of . camphor and ammonia chloride get liquefied on mixing with each other. These reactions may be noticed by precipitation effervescences. menthol camphor and ammonium chloride are triturated together to form liquid. Chemical incompatibilities often occur due to oxidation –reduction. To dispense this prescription.Example: Menthol 5g Camphor 5g Ammonium chloride 30g Light magnesium carbonate 60g In this prescription menthol. The chemical interaction can be minimized by changing the order of mixing or mixing the solutions in dilute forms but no alteration is made in the formulation. CHEMICAL INCOMPATIBILITY IS TWO TYPES: 1) Tolerated: In tolerated incompatibilities. decomposition. colour change or by explosion. Acid base hydrolysis or combination reaction. CHEMICAL INCOMPATIBILITY Chemical incompatibility may be as a result of chemical interactions between the ingredients of a prescription and a toxic or inactive product may be formed. Add light magnesium carbonate and mix it thoroughly to make free flowing powder.

PRECIPITATE YIELDING INTERACTIONS The precipitate form through the chemical incompatibility may be diffusible or indiffusible. Weigh a suitable quantity of compound tragacanth powder (2g per 100 ml of finished product) . METHOD (B) The method is followed when indiffusible precipitates are formed in large quantity. Dissolve one of the reacting substances in one of the portion and the other in the other portion. Example: Caffeine citrate can be substituted with caffeine in sodium salicylate and caffeine citrate mixture. Divide the vehicle into two portions. The method A and B is followed in dispensing the prescription yielding diffusible and indiffusible precipitates respectively. Dissolve one of the reacting substances in one portion.a prescription with another of equal therapeutic value. Divide the vehicle into two equal portions. Mix the two portions by slowly adding one portion to the other by rapid stirring. UNINTENTIONAL: When the prescriber prescribes the drugs without knowing that there is incompatibility between the prescribed drugs. CHEMICAL INCOMPATIBILITY MAY BE: INTENTIONAL: When the prescriber knowingly prescribes the incompatibility drugs. METHOD (A): The method is followed when diffusible precipitates are formed in very small quantity.

and transfer in a mortar and use part of second portion of vehicle to produce smooth mucilage. Example: Strychnine hydrochloride solution 6 ml Aromatic spirit of ammonia 4 ml Water make up to 1200 ml Strychnine hydrochloride is an alkaloidal salt were as aromatic spirit of ammonia is an alkaline substance.Alkaloidal salts with alkaline substances: Alkaloids are weak bases. Then add other reacting substances. Ammonium bicarbonate. such as. If these salts are dispensed with alkaline preparations. solution of ammonia. When they react together. the strychnine get precipitated because the quantity of strychnine hydrochloride prescribed in the prescription is much more than its solubility in water (1 in 7000). They are almost insoluble in water but alkaloidal salts are soluble in water. A secondary label“shake the bottle before use” should be fixed on the container whenever method A or method B is followed in dispensing the prescription. aromatic spirit of ammonia. 1. The aromatic spirit of ammonia contains negligible amount of alcohol which can nor . Mix the two portions by slowly adding one portion to the other with rapid stirring. strong solution of ammonium acetate. the free alkaloid may be precipitated.

carbon dioxide gas is liberated due to the following reaction. Hence follow method A for precipitate yielding combination. the two reacting substances must be dispensed separately. following steps may be taken to avoid this chemical change. Bismuth sub nitrate when combined with sodium bicarbonate when combined with sodium bicarbonate in the presence of water. KCIO3 + 3FeI2 3FeOI +3I+KCI To prevent the incompatibility. CHEMICAL INCOMPATIBILITY CAUSING EVALUTION OF CARBONDIOXIDE GAS. Hence.dissolves the strychnine. 4. Hence it gets precipitated as diffusible precipitates. 2BiONO3 +2NaHCO3 . free iodine is liberated. SOLUBLE IODIDES INCOMPATIBILITIES: Iodides undergo oxidation forming iodine which is an undesirable product. SOLUBLE SALICYLATE INCOMPATIBILITIES: Soluble salicylate with ferric salt: Ferric salt reacts with sodium salicylate to liberate indiffusible precipitates of ferric salicylate therefore follow method B for precipitate yielding interactions. Example: Oxidation of iodides with potassium chlorate: When soluble iodides react with potassium chloride. Example: Ferric chloride solution 2ml Sodium salicylate 3g Water make up to 90 ml 3. Hence it gets precipitated as diffusible precipitates. 2.

a polyvalent soap is formed which inverts the emulsion. 6. The phenolphthalein dye is colorless in acid solution but red in alkaline mixture.COLOUR STABILITY OF DYES: The colour of the most of the dyes used in pharmaceutical formulation is influenced by their ionization which depends on PH of the solution. ammonia and triethanoamine soaps are incompatible with salts producing polyvalent cations.(BiO)  2CO3 + 2NaNO3+CO2+H2O 5. . Due to double decomposition.INCOMPATIBILITY OF EMULSIFYING AGENTS: Emulsion prepared with alkali metal.

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