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Questions and Answers
What is defined as the undesired changes in the properties of a medicament when two or more ingredients are mixed?
What is defined as the undesired changes in the properties of a medicament when two or more ingredients are mixed?
Which type of incompatibility involves a decrease in solubility or loss of potency?
Which type of incompatibility involves a decrease in solubility or loss of potency?
What can result from unresolved pharmaceutical incompatibility?
What can result from unresolved pharmaceutical incompatibility?
Which of the following is NOT a common cause of physical incompatibility?
Which of the following is NOT a common cause of physical incompatibility?
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Which of the following is an example of an insoluble substance in water?
Which of the following is an example of an insoluble substance in water?
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What is a suggested corrective action for a substance that is insoluble in a solvent?
What is a suggested corrective action for a substance that is insoluble in a solvent?
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What can be a result of complexation during the mixing of drug substances?
What can be a result of complexation during the mixing of drug substances?
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Which ingredient change may help correct a situation of insolubility?
Which ingredient change may help correct a situation of insolubility?
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What phenomenon occurs when low melting solids mix to form a liquid at room temperature?
What phenomenon occurs when low melting solids mix to form a liquid at room temperature?
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Which of the following agents can be used to address incompatibility due to solid liquefaction?
Which of the following agents can be used to address incompatibility due to solid liquefaction?
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Which type of incompatibility is characterized by immediate visible changes such as effervescence or precipitation?
Which type of incompatibility is characterized by immediate visible changes such as effervescence or precipitation?
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What can accelerate the oxidation of pharmaceuticals in a mixture?
What can accelerate the oxidation of pharmaceuticals in a mixture?
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Which of the following is NOT a typical cause of chemical incompatibility?
Which of the following is NOT a typical cause of chemical incompatibility?
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Which group of substances can undergo auto-oxidation, compromising their stability?
Which group of substances can undergo auto-oxidation, compromising their stability?
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What is the outcome when two pharmaceuticals form an insoluble substance in a solution?
What is the outcome when two pharmaceuticals form an insoluble substance in a solution?
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Which of the following compounds is likely to be oxidized if exposed to heat?
Which of the following compounds is likely to be oxidized if exposed to heat?
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What can flocculent precipitation several days after preparation indicate?
What can flocculent precipitation several days after preparation indicate?
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What gas may be formed due to the acid-base reaction between ammonium carbonate and oxymel?
What gas may be formed due to the acid-base reaction between ammonium carbonate and oxymel?
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Why does salicylic acid precipitate in the presence of citric acid from syrup of lemon?
Why does salicylic acid precipitate in the presence of citric acid from syrup of lemon?
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How can you correct the incompatibility caused by the formation of salicylic acid?
How can you correct the incompatibility caused by the formation of salicylic acid?
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How do alkaloids precipitate in the presence of tannins?
How do alkaloids precipitate in the presence of tannins?
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What is a potential therapeutic incompatibility issue when dosing medications?
What is a potential therapeutic incompatibility issue when dosing medications?
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What type of precipitation occurs when morphine hydrochloride is in a basic media?
What type of precipitation occurs when morphine hydrochloride is in a basic media?
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What effect does pH have on the solubility of weak bases like alkaloids?
What effect does pH have on the solubility of weak bases like alkaloids?
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Study Notes
Incompatibility in Pharmaceutics
- Incompatibility refers to undesired changes in the physical, chemical, or therapeutic properties of a medication when two or more ingredients are mixed
- Incompatibilities can arise during compounding, dispensing, or administration
- Incompatibilities are easier to prevent than to correct, saving time, materials, and money
Types of Incompatibility
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Pharmaceutical incompatibility - This can be categorized as physical or chemical:
- Physical incompatibility includes decreased solubility (precipitation), loss of potency, and changes in physical characteristics
- Chemical incompatibility leads to chemical instability and complexation, often occurring in solutions or even solids
- Therapeutic incompatibility - This occurs when pharmaceutical incompatibility isn't corrected, leading to altered or reduced therapeutic effectiveness
Physical Incompatibility
- Involves interactions between two or more substances that lead to changes in color, odor, taste, viscosity, and morphology
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Insolubility - The solvent may be insufficient or inappropriate. Heating to increase solubility may be ineffective, as the substance may precipitate on cooling.
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Examples
- Silicon is insoluble in water
- Gums are insoluble in alcohol
- Resins are insoluble in water
- Phenobarbital is insoluble in water
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Examples
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Correction
- Alter the solvent used (e.g., switch to alcohol instead of water).
- Change the form of ingredients (e.g., use sodium phenobarbital instead of phenobarbital).
- Adjust the volume of the prescription or solvent (e.g., increase the volume of alcohol in an elixir or water). Dose adjustment may be necessary.
- Formulate a suspension using a suspending agent.
- Add a complexing agent (e.g., potassium iodide (KI) to dissolve iodine (I2) in water).
- Precipitation - Salting out of camphor and volatile oils from aromatic waters when a salt is dissolved in the aromatic water.
- Separation of Immiscible Liquids - Oils dissolved in alcohol separate as a layer when water is added. This can be corrected by using an emulsifying agent and forming an emulsion.
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Liquefaction of Solid Ingredients - This incompatibility occurs due to the formation of a eutectic mixture.
- Eutectic Mixture - Some solids with low melting points, when mixed, will have a lower melting point than the individual components. This can lead to liquefaction at room temperature. Common examples include camphor, menthol, phenol, thymol, and chloral hydrate.
- Example - Aspirin and aminopyrene. This can be corrected by adding light magnesium oxide or magnesium carbonate as an adsorbent and diluent.
Chemical Incompatibility
- Usually results from chemical interactions among prescription ingredients
- Immediate Incompatibility Occurs immediately upon compounding and is readily apparent due to effervescence, precipitation, or color changes.
- Delayed Incompatibility May occur later and may or may not result in loss of therapeutic activity.
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Types
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Oxidation - Certain prescription mixtures may be oxidized when exposed to air, excessive storage temperature, light, over-dilution, incorrect pH adjustment, or the presence of catalysts like heavy metal ions (Fe+3, Fe+2, Cu+2, Cr+3), as well as bacterial or mold enzymes.
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Examples
- Compounds that undergo oxidation by heat (e.g., adrenaline, phenylephrine, and dextrose).
- Compounds that undergo oxidation by light and catalysts (e.g., sulfacetamide eye drops, sulfonamide injections).
- Compounds that undergo auto-oxidation (e.g., oils and fats, phenolic substances, aldehydes, and vitamins). Antioxidants are often used to prevent auto-oxidation.
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Examples
- Reduction - Less common in prescriptions. Silver salts may be reduced to metallic form by light.
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Precipitation - When two or more pharmaceuticals are combined, an insoluble substance may form and precipitate from solution.
- Flocculent precipitation (which develops several days after preparation) may be due to delayed incompatibility but more frequently indicates yeast, mold, or bacterial growth. Such growth may be caused indirectly by chemical incompatibility if the preservation system is inactivated by chemical reactions.
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Evolution of a Gas - A gas may be formed by a chemical reaction between ingredients.
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Examples - The effervescence caused by the liberation of CO2 from:
- The reaction of carbonates and acids in aqueous media.
- Decomposition of syrups of para-amino salicylic acid.
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Examples - The effervescence caused by the liberation of CO2 from:
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Gelatinization - Solutions may form a gel when combined with certain substances.
- Example - Acacia solutions are gelatinized by ferric salts.
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Precipitation Due to pH Changes
- Example - Morphine hydrochloride and other alkaloidal compounds are weak bases and are soluble in acidic media but precipitate in basic media.
- Alkaloids also precipitate in the presence of tannins (found in cardamom, hamamelis, cinchona, cinnamon, and tea). Tea in high concentration is used to precipitate alkaloids and prevent absorption in cases of alkaloid poisoning.
- Iron salts precipitate in the presence of tannic acid. The precipitate is dark in color, depending on the amount of tannic acid present.
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Oxidation - Certain prescription mixtures may be oxidized when exposed to air, excessive storage temperature, light, over-dilution, incorrect pH adjustment, or the presence of catalysts like heavy metal ions (Fe+3, Fe+2, Cu+2, Cr+3), as well as bacterial or mold enzymes.
Incompatibility Examples
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Rx1
- Ammonium carbonate or bicarbonate
- Oxymel
- Water
- Incompatibility - Formation of gas CO2 due to an acid-base reaction (oxymel is a weak acid due to the presence of acetic acid).
- Correction - Control the reaction during mixing by using an open container until the reaction stops.
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Rx2
- Sodium salicylate 5 gm
- Syrup of lemon 20 ml
- Water Q.S to 75 ml
- Incompatibility - One of the components of syrup of lemon is citric acid, which converts sodium salicylate to salicylic acid (due to a decrease in pH). Salicylic acid has low solubility in water and will precipitate.
- Correction - Prevent this by using tincture of lemon with simple syrup instead of syrup of lemon, or changing the syrup to a suspension using a suspending agent.
Therapeutic Incompatibility
- Can occur due to overdosing or improper dosage of a single drug.
- Example - An infant may require a 125 mg antibiotic dosage, while children and adults require 250 mg or higher dosages (500 mg for adults). Giving adult dosages to infants could be dangerous.
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Description
This quiz explores the concept of incompatibility in pharmaceutics, focusing on its types, including physical, chemical, and therapeutic incompatibilities. Understand the importance of addressing these issues to prevent undesired changes in medication effectiveness and properties. Test your knowledge on how these incompatibilities can be identified and managed.
