Unit 2 - Rectal delivery 2 Flashcards
What are the ideal properties of a suppository base?
- rapid release of drug in active form
- patient acceptability
- ease of manufacture
- stability during storage (fatty bases)
Why is rapid release of drug active form in a suppository important?
- either melts at body temperature or dissolve in rectal fluids to release drug within 10 minutes
- compatibility with a broad variety of drugs (no chemical reaction or complex formation)
- good wetting, emulsifying properties
What factors are important for patient acceptability in suppositories?
- neither toxic, sensitising, nor irritant to rectal mucosa
- capable of being handled and firm enough for easy application
- bland
What factors are important for manufacturing suppositories?
- easily moulded by pouring
- adequate shrinkage allowing easy removal from mould without lubricant
- good suspending power for heavy insoluble medicaments
- stable above melting point
What can higher melting point suppository bases be used for?
Drugs that lower the melting point of the base - camphor - chloral hydrate - menthol - phenol - thymol - volatile oils Or when formulating suppositories in tropical climates
When can lower melting point suppository bases be used?
When adding materials that will raise the melting points or if adding large amounts of solids
What are the two methods in preparing suppositories?
- moulding
- compression
How are suppositories moulded?
- melt base
- incorporate ingredients
- pour into mould (overfill)
- allow to cool
- remove from mould
Give examples of suitable bases that can be used to make suppositories
- cocoa butter
- hard fats
- glycerinated gelatin
- PEGs
Describe suppository moulds
- commonly made from metal or plastic
- care must be taken in cleaning and drying
- lubrication may be required (glycerinated gelatin)
- calibration may be required
How are suppository moulds calibrated?
- pour base into mould
- cool and trim
- remove suppository and weigh
- divide total weight by the number of blank suppositories prepared to obtain the average weight of each suppository for this particular base
How is the melt prepared for a suppository base?
- use the least possible heat
- incorporate medicament
- pour close to congealing point
- pour continuously to avoid layering
- overfill mould
How is the drug prepared for a suppository?
- comminuted to a uniform, small particle size
- maximum quantity of drug/excipient to be incorporated is 30% of the blank weight of the suppository
- liquids may occupy too much volume to be easily incorporated
- if a large quantity of liquid is to be incorporated into an oily suppository base, a water-in-oil emulsion may be required
How is a drug be mixed and poured to make a suppository?
- sufficient mixing to obtain a uniform distribution of the drug
- slowly fill cavity, avoiding air bubbles, leaving a small excess of material on the top of the mould
- do not stop the pouring process until the mould is filled
How are suppositories cooled and finished?
- set at room temperature or by refrigeration (if necessary)
- remove excess material to leave a nice smooth surface on the suppository
- remove carefully from the mould, package and label
How are suppositories compressed?
- incorporate ingredients vigorously
- force into mould using compression machinery
- remove from mould
What is compression manufacture of suppositories suitable for?
- bases that can be formed into suppositories under pressure
- useful for heat labile medicaments and where there is a large amount of insoluble material
What are the limitations in compression manufacture of suppositories?
- special machinery required
- limitation to suppository shape
- air entrapment
- slow
What are the problems in suppository preparation?
- moisture in suppositories
- hygroscopicity
- incompatibilities
- viscosity
- brittleness
- volume contraction
- rancidity
Why should water be avoided in suppositories?
- accelerates oxidation of fats
- crystallises materials on evaporation
- increases reactions between ingredients
- assists bacterial growth
Why is hygroscopicity a problem in suppositories?
Irritable for patient
Why is viscosity important in suppository manufacture?
- controls sedimentation
- control temperature or add viscosity enhancer e.g. aluminium monostearate or increase fatty acid chain length
What factors cause brittleness in suppositories?
- synthetic fatty bases most brittle
- can be induced by rapid cooling
- reduced by Tweens (increase plasticity)
Why is volume contraction important in making suppositories?
- required to eject suppository
- undesirable at base of suppository (overfill)
Why is rancidity important in making suppositories?
- resistance of the fatty base to oxidation measured by quantity of peroxide
- may require an antioxidant
What appearance factors are important when making suppositories?
- odour
- colour
- surface condition
- shape
What factors are used to check quality control in making suppositories?
- appearance
- weight
- disintegration time
- mechanical strength
- content uniformity
- drug release from suppositories
What weight factors are important when making suppositories?
BP limits:
- weigh 20 suppositories individually and together
- no more than 2 > 5% deviation form average weight
- none deviate > 10%
How is disintegration time used to check for quality when making suppositories?
- complies with BP disintegration test for suppositories and pessaries
- does not relate to suppositories intended for modified release
When is disintegration acheived?
When suppository is:
- dissolved or
- separated into component parts
- softened (no solid core)
What are the time limits for disintegration of a suppository?
Fatty base - no more than 30 mins
Water soluble base - no more than 60 mins
Pessaries - no more than 60 mins
What is the temperature of the rectum?
Not necessarily 37C
- implications for drug release from suppositories
What other local rectal formulations are available?
- ointments/creams (e.g. haemorrhoids)
- enemas (aqueous or oily suspensions or solutions for evacuations /X-ray diagnosis)
What other systemic rectal formulations are available?
- tablets - do not disintegrate well in low volume of rectal fluid
- capsules - soft shell, contents solid at room temperature. Similar release profile to suppositories - suitable for tropical climates. Special machinery required
- micro-enemas - rapid bioavailability but costly and difficult to administer
- retention enemas
- large volume enemas
