Lab 8

What does pharmaceutical stability include?

Active ingredients, excipients, containers, and storage conditions.

How does the USP define pharmaceutical stability?

The extent to which a product retains its original properties and characteristics within specified limits throughout its shelf life.

What is shelf life?

The period during which a pharmaceutical product maintains its required stability during storage and use.

• should not be less than 95%

• p-aminophenol should not be more than less than or equal to 1%

What are the five types of pharmaceutical stability?

Chemical, physical, microbiological, therapeutic, and toxicological.

What is chemical stability?

Each active ingredient retains its chemical integrity and labeled potency within specified limits.

What is physical stability?

The product retains its original appearance, palatability, uniformity, dissolution, and suspendability.

What is microbiological stability?

Sterility or resistance to microbial growth is maintained, and antimicrobial agents remain effective.

What is therapeutic stability?

The therapeutic effect of the drug remains unchanged.

What is toxicological stability?

No significant increase in toxicity occurs.

Which physical properties must remain stable?

Appearance, palatability, uniformity, dissolution, and suspendability.

What processes affect pharmaceutical stability?

Manufacturing, packaging, storage, distribution, and use.

How is pharmaceutical quality maintained?

By evaluating and monitoring all processes and testing products under normal and stress conditions.

What are the five common degradation reactions?

Hydrolysis, oxidation, photolysis, dehydration, and racemization.

How can the rate of degradation be predicted?

By the number of reacting species or the order of the reaction.

What is incompatibility?

Preventable physical or chemical reactions that can be minimized or eliminated through corrective measures.

When should incompatibilities be evaluated?

During formulation design by evaluating physical and chemical properties.

What is an example of physical incompatibility?

A pH change causes a soluble ionized drug to precipitate during preparation or storage.

What is an example of chemical incompatibility?

Heavy metals in water catalyze oxidation of penicillin, epinephrine, and phenylephrine.

How does EDTA reduce oxidation?

EDTA chelates heavy metals to prevent metal-catalyzed oxidation.

How does increased temperature affect drug stability?

It accelerates oxidation, reduction, and hydrolysis.

How much does reaction rate increase for every 10°C rise?

The rate is estimated to double or triple.

How does increased temperature cause evaporation?

It increases the loss of water and volatile solvents.

Why are volatile solvents used in pharmaceutical products?

To solubilize nonpolar drugs, dyes, flavors, and aromatic oils.

What happens when volatile solvents evaporate?

Supersaturation, precipitation or crystallization, and changes in color or odor.

How can light indirectly affect stability through temperature?

Light raises product temperature, increasing evaporation and instability.

What are photolabile substances?

Substances that degrade when exposed to light.

What factors affect the rate of photodegradation?

Light intensity and wavelength; container size, shape, composition, and color.

Why is ultraviolet radiation especially damaging?

Its high energy makes photoinstability and photo-oxidation more likely.

How does light cause oxidative degradation?

It forms free-radical intermediates that  initiate oxidation chain reactions.

How can light-induced oxidation be reduced?

By using antioxidants and chelating agents.

How do colored containers protect light-sensitive formulations?

Yellow-green glass provides the best UV protection; amber protects considerably against UV but little against infrared.

What are examples of photolabile drugs or chemicals?

Nitroprusside, epinephrine, vitamins, riboflavin, and p-aminophenol.

How does moisture affect pharmaceutical stability?

Water content influences oxidation, hydrolysis, and reduction.

What factors affect the rate of hydrolysis?

Water content, temperature, and pH.

Which functional groups are susceptible to hydrolysis?

Esters, amides, imides, imines, and lactams.

Which drugs are most prone to hydrolysis?

Esters and beta-lactams such as penicillins; amides such as acetaminophen are less susceptible.

What is zero-order hydrolysis?

Degradation occurs at a constant rate independent of drug concentration.

How does concentration affect zero-order hydrolysis?

Higher concentration decreases the percentage decomposed; dilute solutions lose a greater proportion.

What is first-order hydrolysis?

The degradation rate is directly proportional to drug concentration.

How does increasing concentration affect first-order hydrolysis?

It does not change the percentage decomposed over a given time.

What is hygroscopicity?

The tendency of a substance to readily absorb moisture from the environment.

What happens when hygroscopic substances absorb water?

They may liquefy into a jelly-like material and support microbial growth.

What determines water content in pharmaceutical preparations?

Moisture in raw materials and water used as a solvent.

What conditions promote microbial growth?

Ineffective preservatives and increased water content, especially under high-humidity storage.

How does pH affect drug stability?

It influences solubility and the rate of degradation or decomposition.

Which factors are most likely to cause clinically significant drug loss?

pH changes and elevated temperature, mainly through hydrolysis and oxidation.

What is the hydrolytic degradation product of acetaminophen?

p-Aminophenol.

What reagent detects p-aminophenol?

Alkaline sodium nitroprusside solution.

What color forms when p-aminophenol reacts with alkaline sodium nitroprusside?

Bluish-green.

What instrument detects the color change from p-aminophenol?

A spectrophotometer (multiwell plate reader).

What is the USP limit of p-aminophenol in acetaminophen?

0.005% w/w relative to acetaminophen concentration.