Chemical And Physical Stability

Question 1

Admixture

Answer 1

Combined Parenteral dosage forms for administration, including SVPs and LVPs

Question 2

Incompatibility

Answer 2

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

Question 3

Chemical incompatibility

Answer 3

More rapid degradation
Hydrolysis
Oxidation
Photolysis
Increased storage temperature
Packaging

Question 4

Hydrolysis

Answer 4

Ph catalyzes hydrolysis

Question 5

Order of liability to hydrolysis:

Answer 5

B-lactams, esters, imines, and amides

Question 6

Oxidation

Answer 6

Free radical react with oxygen or loss of electrons, often catalyzed by trace metals

Question 7

Oxidation signs

Answer 7

Coloring on the drug

Question 8

Oxidation effects

Answer 8

fats and natural oils

Question 9

Antioxidants

Answer 9

Tocopherol
EDTA
Sulfites
Nitrogen blanket

Question 10

Photolysis

Answer 10

Decomposition of drug by light

Question 11

Avoiding photolysis

Answer 11

Amber vials
Aluminum foil

Question 12

Photolysis affects

Answer 12

Tryptophan

Question 13

Chemical incompatibility

Answer 13

Increases over time
Depends on vehicle

Question 14

Physical incompatibility

Answer 14

Interactions of two or more substances
Change in appearance
Change in color
Chang in clarity
Evolution of gas
Combining anions and cations can lead to precipitation

Question 15

Salting out

Answer 15

High levels of salts lead to precipitation
Dehydrate nonelectrolytes (neutral) and electrolytes (ion pairs)

Question 16

Isoelectric point

Answer 16

PH where molecule has no net charge. Protein has lowest solubility and highest adsorption at isoelectric point.

Question 17

albumin isoelectric point

Answer 17

4.9

Question 18

Adsorption

Answer 18

Lipophilic drugs partition into plastic and rubber at container surfaces

Question 19

Freeze drying

Answer 19

Reduced water content, enhanced drug stability
High storage stability for biologics

Question 20

Drug solubilization

Answer 20

Removal of molecule from crystal lattice
Creating a void in solvent
Release of solvation energy

Question 21

nonpolar drugs and solubility

Answer 21

Poor water solubility due to hydrophobic effect
Water forms a highly ordered shell reducing mobility

Question 22

Hydrophobic effect

Answer 22

Adsorption
Assembly
Particle aggregation
Embolization

Question 23

Ionizable drug and solubility

Answer 23

PH adjustment can increase water solubility
Weak acids increased at pH>5
Weak bases increased at pH <7

Question 24

To maintain pH in solution

Answer 24

Use buffers

Question 25

Account for >90% of cations

Answer 25

Sodium salts of weak acids

Question 26

Most common salts

Answer 26

Hydrochloride salts of weak bases

Question 27

IV dilution in salts

Answer 27

Rapid and neutralizing

Question 28

IM salt dilution

Answer 28

Reduced

Question 29

SC salt dilution

Answer 29

Further reduced, more potential for irritation

Question 30

Cosolvent solubility

Answer 30

Reduces polarity Usually diluted with normal saline and infused as diluted solution Use of final filter recommended

Question 31

Cosolvents

Answer 31

Propylene glycol Ethanol Glycerol Polyethylene glycol Dimethylacetamide

Question 32

Rapid IV of propylene glycol

Answer 32

Hypotension Arrhythmias Thombophlebitis

Question 33

Cosolvents for IM

Answer 33

Precipitation may occur in cosolvent formulation after IM injection Slow and erratic drug absorption

Question 34

Nonionic surfactant

Answer 34

Molecule that has water-loving and water hating parts Surface active Reduce surface tension of water Potentially adsorb the surface Forms a micelle at higher concentrations

Question 35

Micelle vs liposomes

Answer 35

Liposomes have a hole in the center

Question 36

Taxol

Answer 36

Surfactant Solution is diluted prior to infusion and forms a super-saturated solution which may precipitate

Question 37

Cremophor-EL

Answer 37

Widely used nonionic surfactant Enhances leeching of additives from PVC Allergic reactions in later doses Pgp responsible for multi-drug resistance Influences PK of paclitaxel

Question 38

Increase solubilization

Answer 38

PH adjustments Co-solvents Micelles Complexes Prodrugs Nanoparticles Emulsions

Question 39

drug solubilization

Answer 39

pH adjustments/salts cosolvents micelles complexes prodrugs nanoparticles oils/emulsions

Question 40

solubility of drug complexes

Answer 40

=solubility of complexed drug + concentration of drug in complexed drug

Question 41

cyclodextrans

Answer 41

relatively nontoxic cyclic oligomers of dextrose that form complexes with drugs

Question 42

Prodrugs for injection

Answer 42

--Prodrug containing a hydroxyl, carboxyl, or amine form hydrophilic prodrugs to enhance solubility --After IV pro-moiety is removed by hydrolysis or esterase --may alter the PK of parent drug depending on rate of prodrug conversion to parent drug

Question 43

Etopophos

Answer 43

Prodrug: water solubility of etoposide phosphate lessens potential for precipitation after dilution during IV infusion

Question 44

Nanoparticles for injection

Answer 44

reduced particle size--> increased SA/dissolution solid state: increased drug loading and chemical stability IM, IV, SC

Question 45

nanoparticles

Answer 45

ideal when they are further apart for lower potential energy

Question 46

nanoparticle albumin-bound (abraxane-nab-paclitaxel)

Answer 46

active drug nanoparticle is in non-crystalline, amorphous, readily bioavailable state

Question 47

Long-acting HIV prevention

Answer 47

also uses nanoparticles

Question 48

oil-in-water emulsion

Answer 48

10-20% soybean/sunflower oil 2% glycerol 1% lecithin for oil-soluble drugs