Stability of Medicines

Question 1

What is stability?

Answer 1

Ability to retain the original characteristics during manufacture, transport, storage & use

Question 2

Name the three main factors in product stability

Answer 2

• Physical stability
• Microbial stability
• Chemical stability

Question 3

What might chemical or microbial degradation of a surfactant lead to?

Answer 3

Emulsion cracking

Question 4

Hydrolysis of antimicrobial agent may lead to what?

Answer 4

Loss of protection against microbial spoilage

Question 5

Adsorption into container may lead to what?

Answer 5

Apparent loss of active agent

Question 6

What are physical instabiliteis?

Answer 6

• Change in bioavailability
• Change in medicine form
• Changes in patient acceptability

Question 7

What is polymorphism?

Answer 7

• Different crystal structures
• One stable form (I), one or more metastable forms(II)
• I has highest MP, lowest sol & diss rate

Question 8

What do polymorphic forms affect?

Answer 8

Bioavailability

Question 9

What does conversion occur more rapidly in?

Answer 9

Suspension

Question 10

Particles below 1um and above 1um are what?

Answer 10

<1um = colloids
>1um = coarse suspensions

Question 11

What is instability due to?

Answer 11

Settling

Question 12

Partially soluble drug may change ______ if _____ fluctuates

Answer 12

particle size

temperature

Question 13

What are emulsions?

Answer 13

Dispersion of two immiscible liquids, one evenly distributed as fine droplets in the other (oil in water or water in oil)

• Thermodynamically unstable
• Requires an emulsifying agent

Question 14

What does partial separation of disperse phase lead to?

Answer 14

Creaming in o/w emulsions

Question 15

What does complete separation of phases lead to?

Answer 15

• Cracking
• Irreversible
• Breakdown of emulsifying system

Question 16

Small droplets reduce ______

High viscosity reduces ______

Answer 16

effect

creaming

Question 17

What is pharmacological incompatibility?

Answer 17

opposite effect ‘cancel out’

e.g. b-blockers & salbutamol

Question 18

What is pharmacokinetic incompatibility?

Answer 18

Reduces absorption

e.g. tetracyclines & some antacids

Question 19

What is a drug-excipient interaction?

Answer 19

• Reaction between amino acids & sugars

e. g. maillard reaction between chlorpromazine and dextrose

Question 20

List a physiochemical effect

Answer 20

solvent effect on solubility

e.g. diazepam, poor water solubility

Question 21

List the pH effects on solubility

Answer 21

- Acidic drug: 
Poorly water soluble
pH decreases more drug converted to HA
Solubility decreases 
pH depends on pKa & intrinsic solubility 

• Basic drug
  pH increases more drug converted to B

Question 22

Effect depends upon _____ concentration and _______ solubility

Answer 22

final

intrinsic

Question 23

Supersaturated solutions may not precipitate out immediately, _____ develops in ___ hours

Answer 23

Haze

3

Question 24

What to be aware for in hydrolysis for a given drug?

Answer 24

• Recognition of functional groups in drug

- Comparison of reactivity

Question 25

What affects the rate of hydrolysis?

Answer 25

- pH: specified acid or base catalysed - temperature: all reactions affected - moisture content: humidity, solvent used (reducing water doesn't always reduce hydrolysis) - solubility: dissolved drug reacts much more quickly than solid

Question 26

If R1 groups donate electrons into the carbonyl the ester is less/more prone to hydrolysis

Answer 26

less

Question 27

The _____ of the leaving group affects the rate

Answer 27

stability

Question 28

Are weaker bases/acids better leaving groups

Answer 28

weaker bases if R2 contains an electron withdrawing group it weakens the base and increases the reaction rate

Question 29

Amide hydrolysis mechanism similar to _____ | ____ has major influence

Answer 29

esters | pH

Question 30

Amides are ____ reactive due to more ____ leaving group and less _____ withdrawing effect of ___ in amide compared to ___ in ester

Answer 30

``` less basic electron N O ```

Question 31

In thioesters, which bond is stronger? | S-C or O-C

Answer 31

O-C

Question 32

Better electronic overlap results between atoms of ______

Answer 32

similar size

Question 33

Thioester carbonyl not stabilised by as much ______ as ester carbonyl

Answer 33

resonance

Question 34

Thioester _______ reactive than ester

Answer 34

more

Question 35

What is autooxidation?

Answer 35

Spontaneous oxidation in air at ambient temperatures

Question 36

What is ground state oxygen?

Answer 36

A di-radical

Question 37

Both unpaired electrons in HOMO have same ____ Only singlet oxygen have _____

Answer 37

spin opposite spin

Question 38

Molecular oxygen will react with ___________ (____)

Answer 38

unpaired electrons (radicals)

Question 39

Is oxygen a good/bad initiator

Answer 39

bad

Question 40

Initiation must be able to lose __ or similar to give a relatively _____ _____

Answer 40

H | stable radical

Question 41

List ways to minimise oxidation

Answer 41

- Prevent initiation - Protect from light - Limit peroxides - Use optimum pH (acidic drugs degrade more rapidly when ionised, basic drugs more stable in acidic conditions) - Add chelating agent to remove metal ions - Stop propagation - Exclusion of oxygen (pack under inert gas) - Add antioxidant

Question 42

Give an example of oxidation

Answer 42

ACE inhibitor captopril for children with hypertension - solid dosage form - extemp aq prep which suffer short shelf lives - It undergoes oxidative dimerisation