D11. Chemical stability part 2 Flashcards
Describe oxidation
-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
what is the general definition of oxidation
loss of electrons by a molecule (or hydrogen organic)
what are the two types of oxidation?
-Reversible loss of electrons (can occur in anaerobic conditions)
-Can also involve atmospheric oxygen
what is autoxidation?
Many pharmaceutical oxidations are chain reactions which occur slowly in the presence of O2
ONE NOTE
what is a common feature of drug and ingredient molecules susceptible to degradation?
Many carbon-carbon double bonds, highly conjugated systems, electron rich, lone pair of electrons e.g hydroxyl, carbonyl
how do antioxidants prevent oxidation
-function by providing more electrons (or hydrogen)
-terminate chain reaction and are more easily oxidised than the drug/formulation components
ONE NOTE
how do reducing agents prevent oxidation?
-again more readily oxidized than drug
-e.g. sodium metabisulfite used to prevent decomposition of adrenaline injections
ONE NOTE
what can the air in the container be replaced by to prevent oxidation?
replaced by an inert gas such as nitrogen or carbon dioxide
what is decomposition?
-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
what can happen when light is absorbed, increasing energy state?
-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
the energy of radiation increases with?
decreasing wavelength
e.g u.v > visible > i.r
How do you calculate energy of a wave?
E= hc/ lambda symbol
-Where E= energy (J)
h = Plank’s constant
c=speed of light (ms-1) lambda=wavelength(m)
ONE NOTE
what energy range is responsible for the photodegradation of drugs/ ingredients?
Higher energy range (290 - 390 nm) responsible for the photodegradation of drugs/ingredients
E is directly proportional to what?
1/ lambda (wavelength)
ONE NOTE
what is suitable product packaging against light?
amber glass, cardboard boxes and aluminium foil wrappers
what do trace metals do?
Trace metal ions can catalyse oxidation (and other forms of degradation)
how to prevent trace metal catalysis?
use chelating agents
how do chelating agents work?
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)
what is isomerization?
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
how to prevent isomerization?
-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
when is freeze drying used?
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
what is freeze drying (Lyophilization)?
-removal the moisture from a frozen product under vacuum to preserve integrity
Advantages of freeze drying?
-Low temperatures and vacuum conditions inhibit hydrolysis and oxidation
-The porous solid produced is more readily soluble
Disadvantages of freeze drying?
-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
