Kwon Stability

Half-life (t1/2

Time required for a quantity to reduce to half its initial value

Shelf-life

Time from date of manufacture that a drug product will remain in its approved product specification while stored under defined conditions (12 to 60 months)

Does not mean 100% remaining drug

Specification can mean 95-105%, 90-110%, etc.

Expiry date

Final day that manufacture guarantees the full potency and safety of a drug (Placed on medication labels)

Beyond use date

Date or time after which a compounded sterile preparation (CSP) may not be stored or transported and is calculated from the date or time of compounding

What happens to rate of reaction as temperature increases

increases

For rxns happening at room temp, the rate of reaction doubles for every ______ celcius rise

10 degree

Hydrolysis

o Acid, base, and water catalyzed hydrolysis of drugs

o Order of liability to hydrolysis: β-lactams (cyclic amides), esters, imines, and amides

o Comparing the stability of local anesthetics during steam sterilization, esters (procaine) undergo hydrolysis, whereas amides (lidocaine) remain intact

Most prodrugs are_____ and therefore are susceptible to hydrolysis

Esters

Oxidation

Free radical reactions with oxygen or loss of electrons, catalyzed by trace metals, e.g., epinephrine

o Intact drugs are usually colorless and form colored oxidation products, e.g., pink, amber, blown, black

o Primary cause of the rancidity of fats and natural oils (Triglycerides)

Antioxidants

Tocopherol (Vitamine E)

EDTA: metal chelators

Sulfites: Oxygen scavenger

Where on molecules does oxidation occur

double bonds

Photolysis

o Decomposition of drug by light

o UV light (200-400 nm) has higher energy than visible light (400-750 nm)

o Tryptophan exposed to fluorescent light turns to a blue-green color in 24 to 120 hours in TPN amino acid solutions

Containers to prevent photolysis

Amber vials

Aluminum foil

Admixtures

Combined parenteral dosage forms for administration, including SVPs and LVPs

Incompatibility

Medication error of dosage forms from compounding, dispensing, or administration

Chemcial incompatility

Drug degrades more rapidly after being combined with drugs or formulations

o Hydrolysis

o Oxidation

o Photolysis

o Temperature—Increased storage temperature speeds degradation

Chnace of chemical incompatbility rises with___________

time

pH of 5% dextrose

3.5 to 6.5

Physical incompatibilty def

Interaction of two or more substances that leads to physical changes

Physical incompatibilty signs

Changes in solution appearance

Clarity or turbidity

Color

Precipitation, e.g., dilution of cosolvent

Evolution of gas, e.g., salting out

Examples of physical incompatbilities

Precipitation of unionizable (Neutral) drug after dilution of solubilizing agent

o Addition of IV fluid with acidic pH to a sodium salt of a weak acid: Soluble ionized form → Insoluble non-ionized form

o Combining organic anions and cations

o Heparin is not compatible with ethanol

Salting out

o High levels of salts, > 0.1 M of Ca^2+, K+, Mg^2+, Na+ and Cl^-

o Drug is less soluble in water at high levels of salt

o They dehydrate nonelectrolytes, such as diazepam, causing precipitation as neutral molecules

o They dehydrate electrolytes, such as amphotericin B, causing precipitation as ions pairs

o Immediate release of carbon dioxide gas from carbonated beverages when sodium chloride is added

Absorption

Lipophilic drugs and preservatives in solution partition into plastics and rubber

Adsorption

Drug in solution adhere to a surface

o Plastic surfaces (PVC)

o Filter membranes

o Protein adsorption

Surfactants and proteins love to ______ to surfaces

adsorb

Isoelectric point

pH where a molecule has no net charge

A protein has its lowest solubility at its_____________

isoelectirc point

Stability factors

Drug concentration

Time

Temperature

pH

Watersolubility

Vehicle

Light

Order of mixing

Excipients

Containers