Science of Medicines Week 31

Question 1

define suppository

Answer 1

a solid dosage form intended for administration of a drug via the rectum that melts, softens or dissolves in the body cavity

Question 2

What are examples of diseases the local applications of suppositories treat?

Answer 2

haemorrhoids, itching and infections

Question 3

What are examples of diseases which systemic suppositories can treat?

Answer 3

anti-nauseates, analgesics, hormones

Question 4

How does the physiology of the rectal cavity influence rectal absorption?

Answer 4

1. the quantity of fluid in the rectum for drug dissolution is small, so dissolution is the rate-determining step of absorption
2. rectal fluid is neutral and has no buffer capacity, so drugs must be pH adjusted to stop irritation

Question 5

How are suppositories prepared?

Answer 5

1. drug is dissolved or suspended in a base at a higher temperature
2. the mixture is then poured into a mold
3. solidified at room temperature

Question 6

What are 2 examples of traditional bases used for suppositories?

Answer 6

1. Oil of Theobroma (cocoa butter) - fatty base
2. Glycogelatin - aqueous base

Question 7

What are 2 examples of modern bases used?

Answer 7

1. hydrogenated vegetable bases
2. water-soluble polyethylene glycol (PEG)

Question 8

What are the 3 physical properties of drugs that influence the choice of base?

Answer 8

1. drug solubility
2. drug particle size
3. nature of the base

Question 9

How does drug solubility influence the base used?

Answer 9

1. the rate at which the drug is release from the suppository and absorbed across the rectal membrane is directly related to its solubility in the base
2. need to control the partition coefficient between the base (vehicle) and rectal fluid
3. a drug that is highly soluble in the base will have a low tendency and release rate into rectal fluid

Question 10

How does drug particle size influence the base used?

Answer 10

1. for undissolved drugs in a suppository, the particle size influences its rate of dissolution and therefore absorption (Noyes-Whitney)
2. smaller particles have quicker dissolution and absorption

Question 11

How does the nature of the base affect choice of base?

Answer 11

1. the base must be able to melt, soften or dissolve to release its drug content for absorption
2. if base interacts with drug, absorption may be stopped due to inhibition of drug release
3. if the base irritates the rectal membrane, it may cause bowel movement causing drug release and lack of absorption

Question 12

What are some ideal properties of a suppository base?

Answer 12

1. melts at body temperature
2. non-toxic and non-irritant
3. easily moulded and removed from mold
4. stable when heated above melting point

Question 13

What are the 4 different polymorphic forms of Oil of Theobroma? Which is used for suppositories?

Answer 13

alpha, beta, beta’, gamma - beta is most stable

Question 14

What are the issues with Oil of Theobroma?

Answer 14

1. may become rancid due to oxidation of unsaturated glycerides
2. leakage from the anus as it is immiscible with body fluids
3. melts easily on warming but does not contract on cooling and may be hard to remove from mold
4. EXPENSIVE

Question 15

What is used for oil of theobroma suppositories in hotter climates?

Answer 15

a solidifying agents such as beeswax

Question 16

What are hydrogenated vegetable bases made of?

Answer 16

a mixture of fatty bases with some mono and diglycerides

Question 17

What is a Witepsol?

Answer 17

an example of a hydrogenated vegetable base

Question 18

How can you get an ideal melting range for Witepsols?

Answer 18

using high and low melting point ones mixed together

Question 19

What is the main issue with Witepsols?

Answer 19

they contain emulsifiers, so absorb limited quantities of water and may form o/w emulsions in rectal cavity - poor release of drug

Question 20

What are glycerol-gelatin (glycogelatin) bases made of?

Answer 20

glycerol + water + gelatin

Question 21

What are the 2 uses of glycogelatin suppositories?

Answer 21

1. laxatives
2. vaginal therapy

Question 22

How do glycerol-gelatin bases work in laxatives?

Answer 22

the bases dissolve in the mucous secretions of the rectum and osmosis of water into rectum cause laxative effect

Question 23

How must glycogelatin laxative be stored?

Answer 23

in tight containers as they are hygroscopic

Question 24

What is most common base for macrogols?

Answer 24

PEG (polyethylene glycol)

Question 25

What are benefits of using PEGs as bases compared to fatty bases?

Answer 25

1. melting point can be adjusted 2. release of drug not dependent on melting point 3. physical storage stability is better 4. miscible with rectal fluids

Question 26

What are the drawbacks of PEGs as bases compared to fatty bases?

Answer 26

1. more reactive with drugs 2. release rate of water-soluble drugs will decrease with increasing MW of the PEG used 3. PEGs tend to be more irritating

Question 27

How are suppositories packaged?

Answer 27

in tin, aluminium, paper or plastic to avoid melting or breaking

Question 28

Where are cocoa butter and glycerol-gelatin suppositories best stored?

Answer 28

in the fridge

Question 29

Which 4 size molds are available?

Answer 29

1, 2, 4, and 8 grams

Question 30

What is the issue with formulating suppositories?

Answer 30

1. the mold is filled by volume, but the drug dose is in weight 2. so the capacity of the mold depends on density of the base 3. some suppository is base, some is drug - need to know the drug weight to be added

Question 31

How do we calibrate?

Answer 31

weighing several suppositories of base to be used and adjusting the drug to base ratio

Question 32

If the dose is specified as 'drug weight per suppository', what must we do?

Answer 32

the difference between the suppository made of just base and that with the drug must be determined

Question 33

define displacement value

Answer 33

the value tells you how much of the drug will displace 1g of the base