Which of the following are mechanisms for chemical drug degradation?
hydrolysis
oxidation
isomerization
epimerization
photolysis
vaporization
polymorphism
adsorption
Which of the following are mechanisms of physical drug degradation?
What is the MOST common cause of drug decomposition?
What functional groups are involved hydrolysis reaction drug decomposition?
Ester, Salts, Amides, lactone, lactam
Aldehydes, alcohols, phenols, sugars, alkaloids, unsaturated fats and oils
What factors affect hydrolysis?
temperature
pH
water content
radiation
catalysts
synergists
UV
How would you minimize hydrolysis?
(i) Protecting from heat, (ii) Refrigeration
Adjusting the pH and using buffers
Removing water or reducing water content
Using tightly closed containers
Using an insoluble form of the drug in water
Lyophilization of the product for subsequent reconstitution
Using a soluble form of the drug in water
Applying heat and keep at room temp.
Use open containers
Adding water to dry powder
What causes oxidation?
oxidizing agents
reducing agents
hydrolyzing agents
Free radical may form from the presence of trace amounts of
carbon
calcium
heavy metals (Pb)
peroxides
atmospheric oxygen
carbon dioxide
Which of the following is the initiation stage of free radical formation?
R--R ---> R• + R•
R• + O2 ---> ROO• ROO• + R--R ---> ROOR + R•
R• + R• -----> R--R R• + ROO• ----> ROOR
Which of the following represent the propagation stage of free radical formation?
What factors MOST affect oxidation?
concentration of reducing species
concentration of oxidizing species
Gamma-radiation is used to sterilize products.
Solutions are less sensitive to radiation than solid dosage forms.
Heavy metals (cupric, chromic, ferrous, ferric, etc.) are catalysts that affect hydrolysis.
Epinephrine exhibits a minimum oxidative decomposition at pH = ?
3.4
1.5
2.8
12
7
Epinephrine exhibits a minimum oxidative decomposition at pH 3.4. At higher pH it degrades slower.
In regard to factors affecting oxidation, antibiotic or vitamin preparations have a pH range of maximum stability.
Which antioxidants would be used to improve stability of a drug in an aqueous system?
sodium sulfite
sodium metabisulfite
sodium bisulfite
sodium thiosulfate
ascorbic acid
hydroquinone
propyl gallate
butylated hydroxyanisole (BHA)
butylated hydroxytoluene (BHT)
alpha‐tocopherol
Which antioxidants would be used to improve stability of a drug in an oil system?
For products, extremely sensitive to atmospheric oxygen, the head-space in the pharmaceutical container can be filled with ____ or _____ instead of air.
nitrogen
carbon monoxide
hydrogen
sulfur
water
How would we minimize oxidation other than using antioxidants?
inclusion of chelating agents
buffering agents
water with heavy metals
water without heavy metals
use metal containers
use glass containers
add oxidizing agents
Saturated drug molecules have tendency to interact with lights.
Dextro & Levo optical isomers are pharmaceutically active separately.
Generally dextro forms show more pharmacological effects, e.g., epinephrine, alpha‐methyldopa, propranolol, warfarin, ibuprofen, pilocarpine, ergotamine
Microbiological degradation by bacteria create
alkaline media
acidic media
neutral media
Microbiological degradation by mold and yeast create
Which dosage form is more vulnerable to microbial degradation?
solution preparations
tablets
capsules
topicals
suppositories
To remedy microbiological degradation, preservatives can be added & when alcohol is the vehicle, of ____ alcohol itself gives intrinsic bacteriostatic property.
15‐18%
40-50%
1-5%
7-14%
19-23%
According to the law of mass action, the rate of a chemical reaction is
proportional to the product of the molar concentration of the reactants each raised to a power “usually” equal to the number of molecules, a and b, of the substances A and B, respectively, undergoing reaction.
proportional to the reactants of the molar concentration of the products each raised to a power “usually” equal to the number of molecules, a and b, of the substances A and B, respectively, undergoing reaction.
disproportional to the product of the molar concentration of the reactants each raised to a power “usually” equal to the number of molecules, a and b, of the substances A and B, respectively, undergoing reaction.
inversely related to the product of the molar concentration of the reactants each raised to a power “usually” equal to the number of molecules, a and b, of the substances A and B, respectively, undergoing reaction.
Molecularity is important in reaction kinetics.
One fundamental of kinetics is the reaction equation has to be balanced. Also, termolecular reactions are common.
2 NO + Br2 =2NOBr
unimolecular
bimolecular
termolecular
H2 + I2 = 2HI
Br_2 = 2 Br
The overall order of a reaction is the sum of the _______of the concentration items.
exponents
rate constant
time
[reactants]
[products]
It is difficult to calculate reaction order just looking at the reaction equation.
Knowing reaction order is not important for studying half-life & reaction kinetic studies.
Higher the 'k' value means the slower the reaction.
k does not depend on the concentrations of A & B but it will change if you change the reaction temperature.
All of the following EXCEPT this one are chemical methods of drug degradation.
auto-oxidation
racemization
