Physical and chemical incompatibilities related to non-sterile compounding and reconstitution

Define this:

Physical changes such as precipitation, color change, phase separation, gas evolutio

Physical Incompatibility

Define this:

Chemical reactions between substances causing degradation or loss of potency

Chemical Incompatibility

Define this:

When two drugs together produce an undesirable or harmful clinical effect

Therapeutic Incompatibility

Define this:

Occurs when two solutes are insoluble when mixed.

Precipitation

What is an example of precipitation?

Calcium and phosphate in IV nutrition

How do you prevent precipitation between calcium and phosphate?

Mix phosphate first, add calcium last, and maintain proper pH

Define this:

Two liquids don’t mix (e.g., oil and water).

Common in emulsions and suspensions.

Immiscibility

How do you prevent immiscibility?

Use emulsifying agents like lecithin or acacia

Define this:

Drugs may bind to containers or tubing (usually plastic)

Sorption

What is an example of sorption?

Nitroglycerin and insulin can adsorb to PVC

How do fix nitroglycerin and insulin can adsorb to PVC?

Use non-PVC containers/tubing

What happens when effervescent tablets mix with water?

Gas Formation of CO2

Define this:

Oxidation of epinephrine turns it pink/brown

Color or Odor Change

Define this:

Drug breaks down in presence of water

Hydrolysis

What chemical functional group is this common with?

Esters and Amides

How to prevent hydrolysis?

Use dry storage, mix just before administration.

Define this:

Loss of electrons (increase in oxidation state)

Oxidation

What is oxidation common with?

Vitamin C and epinephrine

How do you prevent the oxidation of Vitamin C and epinephrine?

Add antioxidants (e.g., sodium bisulfite), protect from light

Define this:

Two drugs bind, reducing bioavailability.

Complexation

What does tetracyclines and complexation with?

Calcium, Magnesium and ion

Define this:

A more reactive ingredient replaces another in a salt.

Displacement

What is an example of displacement?

Sodium Bicarbonate and calcium chloride can displace CO2

What are some common ester drug susceptible to hydrolysis?

Aspirin, Procaine, Cocaine, Succinylcholine, and Physostigmine

What are some common amides susceptible to hydrolysis?

Lidocaine, Bupivacaine, Acetaminophen, Pencillin, and Indapamide

What must all non-sterile compounds be labeled with according to USP <795>?

• Beyond-use date (BUD)

• Storage requirements

• Shake well if suspension/emulsion

• "For external use only" for topical formulations

What does reconstitution involve?

Adding a specific diluent to a powdered drug (*Common in antibiotics)

What is the Mnemonic for incompatibility?

HOOP - CD (Hydrolysis, Oxidation, Order of Mixing, Precipitation, Complexation, Diluent Choice)

Define this:

• "Store in refrigerator after reconstitution"

• "Use within 7–10 days"

• "Do not store in humid conditions"

Clues that hydrolysis could affects drug stability

Define this:

• Moisture/humidity

• High or low pH

• Heat

• Aqueous reconstitution

• Extended storage after mixing

Hydrolysis Risk Factors

What is used to mask salty and bitter-tasting drugs?

Effervescence

Define this:

Concentrated solutions of electrolytes are mixed in prescription with solutions of non-electrolytes

Salting-out

Define this:

Aborbs moisture and dissovles

Delliquescent

Define this:

Absorbs moisture but does not dissolve

Hygroscopic

Define this:

Liqueification of solids at room temperature due to lowering of thier melting points

Edutexia

What is oxidiation triggered by?

Prescence of light and oxygen

Which of the following is an example of a physical incompatibility?

A. Oxidation of epinephrine
B. Precipitation when calcium and phosphate are mixed
C. Hydrolysis of aspirin in humid environments
D. Color change from breakdown of riboflavin

B

A pharmacy technician is preparing a TPN solution. Which of the following should be added last to avoid precipitation?

A. Dextrose
B. Calcium gluconate
C. Sodium chloride
D. Potassium phosphate

B

Which of the following pairs is known to cause a chemical incompatibility due to chelation?

A. Acetaminophen and ibuprofen
B. Tetracycline and antacids
C. Warfarin and vitamin K
D. Aspirin and codeine

B (Tetracycline forms insoluble complexes with calcium, magnesium, or iron in antacids.)

A reconstituted antibiotic must be refrigerated and discarded after 10 days. This is because the drug is prone to:

Hydrolysis

Which of the following signs indicates a possible physical incompatibility in a compounded suspension?

A. A sweet odor
B. Separation into layers
C. Mild temperature increase
D. Unpleasant taste

B

Which drug is most likely to be chemically degraded by oxidation?

A. Amoxicillin
B. Latanoprost
C. Epinephrine
D. Omeprazole

C

What is the best method to prevent hydrolysis in an ester-based product?

A. Protect from light
B. Keep in a dry environment and refrigerate if instructed
C. Store in an amber glass bottle
D. Shake well before use

B

A patient reports a “vinegar smell” coming from their aspirin tablets. What has most likely occurred?

A. Sorption
B. Oxidation
C. Emulsification
D. Hydrolysis

D (Aspirin hydrolyzes to acetic acid and salicylic acid)