Stability of pharmaceutical dosage forms

the capacity of a drug substance or drug product to remain within established specifications

stability

what are considered the established specifications of stability

1. identity

2. strength

3. quality

4. purity throughout the retest or expiration dating periods

The word "_____________" literally means "splitting by water"

hydrolysis

hydrolysis is the breaking down of drug in the presence of _________

water

The most likely cause of drug decomposition for drugs from hydrolysis containing

1. esters

2. amides

3. lactones/lactams

order of degradation reactions broken down by hydrolysis the fastest to slowest

Lactam > Ester > Amide > Imide

These hydrolysis reactions usually follow __________ order rate

first

If this hydrolysis reaction occurs due other solvent, it is called ____________

solvolysis

-Loss of electrons -Loss of hydrogen (dehydrogenation)

oxidation

oxidation involves production of ____________ (•O-O•, •OH)

free radicals

The most common is _________________ which involves a free radical chain process

autooxidation

Autooxidation is a ___________________ process -Under the influence of oxygen in air

spontaneous

Degradation of drug by light

photolysis

The ___________ energy range of visible light and U.V. light cause photolysis

higher

example of photolysis is

Degradation of sodium nitroprusside in aqueous solution

photolysis is also common in ______________

steroids

Photolysis is prevented by suitable packing in

1. amber colored bottles

2. cardboard outers

3. aluminum foil over wraps and blisters

Formation of larger molecules like Formaldehyde to paraformaldehyde

polymerization

polymerization is favored at ______ temperature

low

Decomposition of organic acid and release of CO2

decarboxylation

Removal of nitrogen-containing group from organic amines like insulin

deamination

factors affecting hydrolysis and oxidation

1. pH

2. type of solvent

3. complexation

4. surfactants

5. heavy metal

6. light and humidity

The _________________ of a solution has a profound influence on the decomposition of many drugs.

acidity or the alkalinity

Aspirin buffered solution is maximum stable at a pH _________

2.4

Its decomposition is independent of pH between pH __________

5 and 7

Above a pH of __________, the decomposition rate rapidly increases

10

_____________ plays a big role in decomposition

Moisture or water

Replace water with another solvent having lower ___________ constant

dielectric

________________ are examples that can be replaced with water in order to get low degradation

Ethanol and glycols

Complex formation (complexation) ____________ the rate of hydrolysis and oxidation

reduces

___________ agent such as EDTA forms complex with trace metals and reduces oxidative degradation

Chelating

______________ when added to solutions containing drugs form micelle and the drug particles become trapped in the micelle

Surfactants

The hydrolytic groups such as OH- cannot penetrate this micelle cover and reach the drug particles, hence hydrolysis rate is ____________

decreased

Heavy metals such as copper, iron, cobalt and nickel generally catalyze __________________

oxidative degradations

These metals increase the rate of formation of _______________ and enhance oxidative decomposition

free radicals

_______________, especially ultraviolet light enhances photolysis

Light

Humidity enhances ______________ of many drugs, especially the decomposition of drugs sensitive to hydrolytic decomposition.

decomposition

For water sensitive drugs, use what for protection

1. waterproof protective coating

2. tightly closed container

protection against hydrolysis for liquid dosage forms

1. Replacement or reduction of water

2. Reconstitution

3. Store at refrigeration temperature

4. pH

protection against oxidation

1. Keep in dry place

2. Protection against light

3. Use of antioxidants/chelating agents

4. Oxygen-free environment

5. Solid and liquid dosage forms

6. Removal of trace metals

for stabilizing oxidizable drugs

1. oxygen

2. oxidizing agents

3. trace metals

4. light

5. heat

6. other catalyzers