Stability of Medicines

Question 1

Stability

Answer 1

Capacity of a product to remain within specifications to ensure potency, quality or purity

Question 2

Chemical degradation

Answer 2

• Decomposition of chemical moiety
• Due to effects of moisture, oxygen, light & heat
• Results in loss of active drug

Question 3

Physical degradation

Answer 3

• Formulation-specific
• Caking in suspensions, phase separation in emulsions
• Hardness & brittleness of tablets

Question 4

Microbial degradeation

Answer 4

• Microbial contamination
• Metabolism of drug molecule
• Physical spoilage of dosage form
• Infection-causing

Question 5

Drug instability may cause

Answer 5

• Inconsistent dosage
• Undesired change in performance dissolution/bioavailability
• Changes in physical appearance of the dosage form
• Product failures

Question 6

Chemical degradation reactions

Answer 6

• Hydrolysis
• Oxidation
• Photodegradation
• Polymerisation and dimerisation

Question 7

Hydrolysis

Answer 7

• Most common chemical degradation
• Water present in many pharmaceuticals as ingredient or contaminant
• Carboxylic acid derivatives are common in medicines
  Esters and amides

Question 8

Imide

Answer 8

• N-H
• 2 Carbonyal

Question 9

Urea

Answer 9

• 2x NH2
• Carbonyal group

Question 10

Rate of hydrolysis is reduced by

Answer 10

• Dry formulations (powder for reconstitution, solid dosage form)
• Adjusting pH to maximum stability in aqueous solution
• Storage temperature
• Coating
• Choice of packaging

Question 11

Hydrolysis reduction

Complexation

Answer 11

• Caffeine (a xanthine) complexes with local anesthetics, such as benzocaine and procaine

Question 12

Hydrolysis reduction

Surfacant

Answer 12

• Drug molecules become trapped in the micelle
  Hydrolytic groups such as OH cannot penetrate the micelle and reach the drug molecules

Question 13

Oxidation

Answer 13

• Removal of H, loss of e-, addition of O
• Generally occurs via the action of free radicals
• Highly reactive species possessing one or more unpaired electrons
• Generated by the action of light energy (UV), heat or trace metals such as Fe2+ or Cu+

Question 14

Auto-oxidation

Answer 14

• Uncatalysed and proceeds slowly under the influence of molecular oxygen
• Reaction of free radicals with drugs or biomolecules leads to the formation of peroxyl radicals, which initiate and propagate auto-oxidation
• Initiation, Propogation and Termination

Question 15

Prevent auto-oxidation

Remove initiators

Answer 15

Chelation of trace metals with chelating agents: ethylene diamine tetraacetic acid (EDTA), citric acid & tartaric acid

Question 16

Prevent auto-oxidation

Exclude oxygen

Answer 16

Sparge liquids with inert gases such as nitrogen to displace oxygen

Question 17

Prevent auto-oxidation

Add free radicals

Answer 17

• More readily oxidised at lower redox potention

Question 18

Photochemical degradation

Answer 18

• Energy of a photon increases with decreasing wavelength inverse proportional
• UV light has high energy which can catalyse reactions
• UV light could cause oxidation, polymerisation
• Ring rearrangement

Question 19

Polymerisation

Answer 19

• A process by which two or more identical drug molecules combine together to from a complex molecule
• UV radiation induces the polymerisation of chlorpromazine

Question 20

Photolysis

Answer 20

• Decomposition by light
• last for a year without light
• 4 hours with light

Question 21

Prevent photolysis

Answer 21

• Exclude from light
• Packaging in foil
• Filter out light by
• Storage in amber glass or Coating tablets with pigmented polymers

Question 22

Zero order reaction

Answer 22

• Degradeation of drug increases as time increases regardless of concention of drug

Question 23

First order

Answer 23

• Degradeation directally proportional to it concentration
• ln() funtion then it is first order

Question 24

Pseudoreaction

Answer 24

• lots of solid dissolving degrade dependant on concentration but regardless of concentration
• Initially zero order to first

Question 25

Second order

Answer 25

- The rate of degradation of A is directly proportional to its concentration and the concentration of the reactant B - Length of half life increases with decreasing concentration

Question 26

# Acceptable degradeation Toxicity of degradation products

Answer 26

Antifungal drug flucytosine degrades to fluorouracil (cyctotoxic)

Question 27

# Acceptable degradation Physical properties of dosage form

Answer 27

Irreproducible dose

Question 28

# Acceptable degradation Aesthetics (look & feel)

Answer 28

Adrenaline degrades to red adrenochrome (unsightly)

Question 29

Acceptable degradedation

Answer 29

5-10% loss of overall limit

Question 30

Expiry date

Answer 30

- Accelerated testing in extream conditions - measure degradation

Question 31

Arrhenius equation

Answer 31

Ae^-Ea/RT

Question 32

Components of Arrenius equation

Answer 32

- ln(a) is y-intercept - Gradient -Ea/R - X intercept 1/T

Question 33

Why Arrhenius?

Answer 33

Duning accelerated testing at high temperature measure degradeation