D11. Chemical stability part 2

Question 1

Describe oxidation

Answer 1

-temperature increases rate of degradation
-Catalyzed by light, trace metals, oxygen and oxidizing agents
-Occurs in both water & oil environments
-can occur in anaerobic environments
-second most common chemical degradation route after hydrolysis for drugs

Question 2

what is the general definition of oxidation

Answer 2

loss of electrons by a molecule (or hydrogen organic)

Question 3

what are the two types of oxidation?

Answer 3

-Reversible loss of electrons (can occur in anaerobic conditions)
-Can also involve atmospheric oxygen

Question 4

what is autoxidation?

Answer 4

Many pharmaceutical oxidations are chain reactions which occur slowly in the presence of O2
ONE NOTE

Question 5

what is a common feature of drug and ingredient molecules susceptible to degradation?

Answer 5

Many carbon-carbon double bonds, highly conjugated systems, electron rich, lone pair of electrons e.g hydroxyl, carbonyl

Question 6

how do antioxidants prevent oxidation

Answer 6

-function by providing more electrons (or hydrogen)
-terminate chain reaction and are more easily oxidised than the drug/formulation components
ONE NOTE

Question 7

how do reducing agents prevent oxidation?

Answer 7

-again more readily oxidized than drug
-e.g. sodium metabisulfite used to prevent decomposition of adrenaline injections
ONE NOTE

Question 8

what can the air in the container be replaced by to prevent oxidation?

Answer 8

replaced by an inert gas such as nitrogen or carbon dioxide

Question 9

what is decomposition?

Answer 9

-decomposition of molecules by the action of light
-Exposure to light of a certain wavelength - results in the absorption of light & increase in energy state

Question 10

what can happen when light is absorbed, increasing energy state?

Answer 10

-may be retained or transferred
-converted to heat
-result in the emission of light (e.g. fluorescence)
-cause decomposition (photolysis – bond breakage) or the generation of free radicals

Question 11

the energy of radiation increases with?

Answer 11

decreasing wavelength
e.g u.v > visible > i.r

Question 12

How do you calculate energy of a wave?

Answer 12

E= hc/ lambda symbol
-Where E= energy (J)
h = Plank’s constant
c=speed of light (ms-1) lambda=wavelength(m)
ONE NOTE

Question 13

what energy range is responsible for the photodegradation of drugs/ ingredients?

Answer 13

Higher energy range (290 - 390 nm) responsible for the photodegradation of drugs/ingredients

Question 14

E is directly proportional to what?

Answer 14

1/ lambda (wavelength)
ONE NOTE

Question 15

what is suitable product packaging against light?

Answer 15

amber glass, cardboard boxes and aluminium foil wrappers

Question 16

what do trace metals do?

Answer 16

Trace metal ions can catalyse oxidation (and other forms of degradation)

Question 17

how to prevent trace metal catalysis?

Answer 17

use chelating agents

Question 18

how do chelating agents work?

Answer 18

capable of forming complex salts with metal ions, by donation of lone electron pairs:
-From a shell around the ion & replace water of hydration
-Ion then inactive in solution (NB not precipitated)

Question 19

what is isomerization?

Answer 19

Process of conversion of a molecule (drug/excipient) into its optical or geometric isomer
e.g. same chemical formula, but placement of substituents/functional groups changed

Question 20

how to prevent isomerization?

Answer 20

-difficult
-Knowledge of conditions in which the isomerization processes occur e.g. extremes of pH, oxidising conditions
-Try to formulate in conditions where these occur slowly

Question 21

when is freeze drying used?

Answer 21

Solutions of some molecules, in particular proteins/peptides, do not have very long shelf-lives even at low temperatures or the presence of water leads to degradation

Question 22

what is freeze drying (Lyophilization)?

Answer 22

-removal the moisture from a frozen product under vacuum to preserve integrity

Question 23

Advantages of freeze drying?

Answer 23

-Low temperatures and vacuum conditions inhibit hydrolysis and oxidation
-The porous solid produced is more readily soluble

Question 24

Disadvantages of freeze drying?

Answer 24

-The porosity, solubility and dryness of the solid make it very hygroscopic (rapidly adsorbs moisture if exposed to the air)
-Can be slow, complicated and expensive
-Relatively difficult for solutions containing non-aqueous solvents