Stability of Medicines

Question 1

define stability?

Answer 1

ability to retain the original characteristics during manufacture, transport, storage and use

Question 2

what are the 3 main factors in product stability?

Answer 2

• physical stability
• microbial stability
• chemical stability

Question 3

chemical/microbial degradation of surfactant may lead to…

Answer 3

emulsion cracking

Question 4

hydrolysis of antimicrobial agent may lead to…

Answer 4

loss of protection against microbial spoilage

Question 5

adoption into container may lead to…

Answer 5

apparent loss of active agent

Question 6

hygroscopic properties may lead to powders liquefying.

what may this lead to?

Answer 6

suppositories losing structure

Question 7

physical instability

change in bioavailability

Answer 7

• alteration of drug solubility

- loss of active through evaporation

Question 8

physical instability

change in medicine form

Answer 8

• separation of liquid phases in emulsions

- setting of solids in suspension

Question 9

physical instability

changes in patient acceptability

Answer 9

• alteration of viscosity
• change in colour, odour, taste
• production of particulate matter

Question 10

what does the polymorph form I have?

Answer 10

highest MP, lowest solubility + dissolution rate

Question 11

if there is crystal growth, what happens to dissolution rate?

Answer 11

slows

Question 12

a use of stable polymorph in chloramphenicol palmitate leads to what?

Answer 12

low blood levels

Question 13

what are particles less than 1m termed?

Answer 13

colloids

Question 14

what are particles more than 1m termed?

Answer 14

coarse suspensions

Question 15

what does stokes law apply to?

Answer 15

course suspensions

large particles settle too quick
small settle too slow and cake

partially soluble drug may change size if temp changes

Question 16

what do small droplets reduce ?

Answer 16

partial separation of disperse phase

Question 17

what does high viscosity reduce?

Answer 17

creaming

Question 18

incompatibility

pharmacological

Answer 18

beta blockers and salbutamol

Question 19

incompatibility

pharmacokinetics

Answer 19

tetracyclines + some antacids

Question 20

incompatibility

apparent interactions

Answer 20

• precipitation
• colour change
• phase separation

Question 21

incompatibility

physicochemical

Answer 21

drug excipient interactions

Question 22

what area of pre-formulation is often overlooked?

Answer 22

Maillard reaction between chlorpromazine + dextrose

Question 23

physicochemical effects

Answer 23

solvent effect on solubility

e. g. diazepam
- poor water solubility
- mixture -> precipitate depending on conc
- 1:10 / 1:20 insoluble
- 1:50 / above clear for 24 hours

Question 24

if acidic drug is poorly water soluble, what happens?

Answer 24

may = given as more water soluble salt (Na / K)

• if pH dec more drug converted to HA
• solubility dec
• pH at which precipitates depends on pKa + INTRINSIC solubility

Question 25

if basic drug is poorly water soluble, what happens?

Answer 25

may = given as more water soluble salt (hydochloride, sulphate) - pH inc -> more drug converted to B

Question 26

what affects the rate of hydrolysis?

Answer 26

- pH - temp - moisture - solubility

Question 27

if the R group donates electrons into the carbonyl, what happens to the ester?

Answer 27

less prone to hydrolysis C2H4Cl reacts faster than C2H5

Question 28

weaker bases are...

Answer 28

better leaving groups

Question 29

phenols are stronger acids than alcohols. if the R groups = phenyl, what happens?

Answer 29

rate inc

Question 30

why is the hydrolysis of amides less reactive?

Answer 30

more basic leaving group + less electron withdrawing effect of N in amide compared to O in ester

Question 31

molecular oxygen

Answer 31

- ground state oxygen = di-radical - both unpaired electrons in HOMO have same spin - singlet oxygen reacts with organic comp (combustion) - molecular oxygen will react with radicals

Question 32

oxidation initiation

Answer 32

- oxygen = not good initiator | - use UV

Question 33

state the C-H bonds, starting with the highest stability

Answer 33

``` benzyl radical allyl radical tertiary radical secondary radical primary radical vinyl radical methyl radical ```

Question 34

how can u minimise oxidation?

Answer 34

- prevent initiation - protect from light - limit peroxides - use optimum pH (acidic drugs degrade more when ionised) - add chelating agent to remove metal ions (EDTA + citric acid) - stop propagation - exclusion of oxygen - pack under inert gas (N) + tablet strips - add antioxidant (ascorbic acid) - chain terminators (BHT act as radical traps)