Chemical And Physical Stability Flashcards
Admixture
Combined Parenteral dosage forms for administration, including SVPs and LVPs
Incompatibility
Medication error of dosage dorms from compounding, dispensing, or administration
Chemical incompatibility
More rapid degradation
Hydrolysis
Oxidation
Photolysis
Increased storage temperature
Packaging
Hydrolysis
Ph catalyzes hydrolysis
Order of liability to hydrolysis:
B-lactams, esters, imines, and amides
Oxidation
Free radical react with oxygen or loss of electrons, often catalyzed by trace metals
Oxidation signs
Coloring on the drug
Oxidation effects
fats and natural oils
Antioxidants
Tocopherol
EDTA
Sulfites
Nitrogen blanket
Photolysis
Decomposition of drug by light
Avoiding photolysis
Amber vials
Aluminum foil
Photolysis affects
Tryptophan
Chemical incompatibility
Increases over time
Depends on vehicle
Physical incompatibility
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
Salting out
High levels of salts lead to precipitation
Dehydrate nonelectrolytes (neutral) and electrolytes (ion pairs)
Isoelectric point
PH where molecule has no net charge. Protein has lowest solubility and highest adsorption at isoelectric point.
albumin isoelectric point
4.9
Adsorption
Lipophilic drugs partition into plastic and rubber at container surfaces
Freeze drying
Reduced water content, enhanced drug stability
High storage stability for biologics
Drug solubilization
Removal of molecule from crystal lattice
Creating a void in solvent
Release of solvation energy
nonpolar drugs and solubility
Poor water solubility due to hydrophobic effect
Water forms a highly ordered shell reducing mobility
Hydrophobic effect
Adsorption
Assembly
Particle aggregation
Embolization
Ionizable drug and solubility
PH adjustment can increase water solubility
Weak acids increased at pH>5
Weak bases increased at pH <7
To maintain pH in solution
Use buffers
Account for >90% of cations
Sodium salts of weak acids
Most common salts
Hydrochloride salts of weak bases
IV dilution in salts
Rapid and neutralizing
IM salt dilution
Reduced
SC salt dilution
Further reduced, more potential for irritation
Cosolvent solubility
Reduces polarity
Usually diluted with normal saline and infused as diluted solution
Use of final filter recommended
Cosolvents
Propylene glycol
Ethanol
Glycerol
Polyethylene glycol
Dimethylacetamide
Rapid IV of propylene glycol
Hypotension
Arrhythmias
Thombophlebitis
Cosolvents for IM
Precipitation may occur in cosolvent formulation after IM injection
Slow and erratic drug absorption
Nonionic surfactant
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
Micelle vs liposomes
Liposomes have a hole in the center
Taxol
Surfactant
Solution is diluted prior to infusion and forms a super-saturated solution which may precipitate
Cremophor-EL
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
Increase solubilization
PH adjustments
Co-solvents
Micelles
Complexes
Prodrugs
Nanoparticles
Emulsions
drug solubilization
pH adjustments/salts
cosolvents
micelles
complexes
prodrugs
nanoparticles
oils/emulsions
solubility of drug complexes
=solubility of complexed drug + concentration of drug in complexed drug
cyclodextrans
relatively nontoxic cyclic oligomers of dextrose that form complexes with drugs
Prodrugs for injection
–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
Etopophos
Prodrug: water solubility of etoposide phosphate lessens potential for precipitation after dilution during IV infusion
Nanoparticles for injection
reduced particle size–> increased SA/dissolution
solid state: increased drug loading and chemical stability
IM, IV, SC
nanoparticles
ideal when they are further apart for lower potential energy
nanoparticle albumin-bound (abraxane-nab-paclitaxel)
active drug nanoparticle is in non-crystalline, amorphous, readily bioavailable state
Long-acting HIV prevention
also uses nanoparticles
oil-in-water emulsion
10-20% soybean/sunflower oil
2% glycerol
1% lecithin
for oil-soluble drugs
