Suppositories Flashcards
What are suppositories?
Solid dosage forms intended for insertion into body orifices (i.e ear, nose, rectum, vagina, urethra)
What are bougies?
Urethral and Nasal bougies are thin and long dosage forms used to insert into urethra and nose respectively.
What are the uses of suppositories?
Carry drug for action at site of placement
Carry drug for systemic action
Disadvantages of suppositories for drug delivery
Strong feeling of aversion in Asians
suppositories can leak
slow onset (~30min) and incomplete drug absorption
considerable intersubject and intrasubject variation in drug absorption
development of proctitis
When will suppositories be recommended for drug delivery?
When patient unable to utilise oral route of drug administration
Also for drugs which are less suited for oral administration (due to high first pass)
What are desirable properties of a suppository base?
Can be moulded by pouring or compression stable if heated above its melting point does not adhere to mould releases drug at desired rate keep its shape when handled and easy to insert does not leak out of orifice into which it is inserted stable during storage non-toxic and non-irritating compatible with drug
What are the different types of bases (include some examples)
Oleaginous bases (fats and oils) water-soluble or water-miscible bases (glycerinated gelatin, PEG) Emulsifying bases (witepsol, massupol)
What are the 3 crystalline forms of theobroma oil? Include their melting points
alpha - unstable, MP of 22-24 deg C
beta - stable, MP of 34 - 36 deg C
gamma - unstable, MP of 18 deg C
How long does it take for unstable alpha form to revert to stable beta form if the theobroma oil was heated above 60 deg C
several days
How to ensure that we obtain beta crystalline forms of theobroma oil
Use low heat of 40-50 deg C and cool slowly.
Disadvantages of theobroma oil base
melting process must monitor carefully
theobroma oil tends to stick to sides of mould
theobroma oil tends to soften in tropical climate and when substances like volatile oils, phenol, or chloral hydrate are added
more difficult to administer as the oil melts on finger tip
theobroma oil tends to leak out of the orifice.
What alternative bases are able to overcome some of the disadvantages of theobroma oil?
Fattibase, suppocire
Will water soluble bases melt?
No, they dissolve slowly in biological fluid
Oppositely charged compounds are incompatible with each other: True or False
True
What does gelatin and glycerin impart on the suppository?
Gelatin: Hardness
Glycerin: Hydrophilicity
Advantages of glycerinated gelatin base?
More prolonged drug release (commonly used in pessaries)
more easily inserted (suitable for urethral administration)
Disadvantages of glycerinated gelatin bases?
Hygroscopic - can lead to dehydrating effect on mucous membrane
Supports the growth of mould
When the proportion of high MW PEG increases in a suppository base, the resultant base will get ______, resulting in a _______ drug release.
Harder, Slower
Advantages of PEG bases?
higher melting point bases can be formulated for convenient storage, easy insertion and no leakage from orifice
bases of varying solubilities can be formulated to control the rate of drug release
Disadvantages of PEG bases?
incompatible with phenols (due to H bonds)
hygroscopic
What is the volume of rectal fluid?
1-3mL, cannot really dissolve suppositories (PEG) very quickly
What are the emulsifying agents in witepsol and massupol respectively?
Monoglycerides and glyceryl monostearate respectively.
advantages of emulsifying bases?
not adversely affected by overheating
solidify rapidly at room temperature
does not adhere to mould
non-irritating
Disadvantages of emulsifying bases?
Unable to release drug very quickly
Rate of drug release is even slower than PEG and Theobroma base
Would hand moulding be used for large scale production of suppositories?
No, it is only used for small scale production
What is a disadvantage of compression moulding?
Entrapment of air in the mould leading to underweight suppository
Types of packaging for suppositories?
Partitioned boxes
screw-capped glass or plastic containers
aluminium foil wrappings
disposable plastic moulds
What are potential problems on storage for suppositories?
Theobroma oil based suppositories could ‘bloom’ and have a white powdery deposit on the surface.
Fat bases could have elevated melting point due to formation of some crystalline forms.
How are suppositories evaluated?
Appearance uniformity of weight uniformity of drug content disintegration time drug release profile mechanical strength melting behaviour
Which of the factors for suppository evaluation are requirements of BP?
uniformity of weight and disintegration time
How is a suppository evaluated for appearance?
sliced lengthwise for examination of colour, surface condition, shape, uniformity of mix
What is the BP method of uniformity of weight evaluation
Take 20 suppositories at random from batch
weigh them individually
Calculate the average weight
This test is not required for moulded suppositories that are required to comply with the test of uniformity of drug content
Acceptance criteria for uniform weight of suppository?
Not more than 2 individual weights deviate from average weight by more than 5% AND
None deviates by more than 10%
Test for uniformity of drug content is used for specific suppositories, how is it tested?
Drug is extracted from the base and assayed using appropriate methods
How many suppositories are tested separately for the disintegration test?
3
What are the acceptance criteria for fat-based and water-soluble suppositories?
Disintegration 30 min or less for fat based
Disintegration 60 min or less for water soluble
What is considered complete disintegration? (3 criterias, satisfying any one is considered complete)
Suppository is completely dissolved
Suppository has dispersed into its component parts
suppository has become soft and the mass has no solid core offering resistance to pressure with a glass rod.
What are the two methods for determining drug release profiles?
Basket method Paddle method (using dialysis membrane)
How can we test for mechanical strength of suppository?
Suppository should be strong enough to withstand the rigours of normal handling.
strength is determine by the amount of weight required to crush the suppository.
What are the two key temperatures to look at the melting behaviour of a suppository?
Softening temperature - the temperature at which deformation occurs
Liquefaction temperature - the temperature at which the suppository melts
Which temperature test is necessary only for suppositories with oleaginous base?
Liquefaction temperature test
What are the chain of effects following the insertion of suppository into the rectum?
For oleaginous base:
Base melts and spreads on mucous lining, followed by sedimentation, wetting and dissolution of drug.
For emulsifying and PEG bases, the suppositories will dissolve and disperse slowly in the rectal fluid.
What is the displacement value of a drug?
refers to the number of parts by weight of a drug which displaces one part by weight of a base
This must be considered in the calculation of the amount of base required for a suppository if the drug content is expressed in terms of weight.
