suppositories Flashcards
suppositories
administration: generally for rectal administration
shape: cylindrical with one/both ends tapered
weight: 1-2g
pessary
administration: generally for vaginal administration
shape: oviform, cone-shaped
weight: 1g
nasal bougie
administration: generally for nasal administration
base: gelato-glycerin base
length: 9-10cm long
weight: 1g
urethral bougie
administration: generally for urethral administration
shape: pencil-shaed (3-6mm diameter, 80mm long)
weight: 1g
ear cone
administration: into the ear
base: oleaginous base
application of suppositories
- carry drug for action at site of placement (eg. emollients, astringents, antiseptics, local anaesthetics)
- carry drug for systemic action (eg. hypnotics, tranquilizers, antispasmodic, antipyretic, antiemetic)
when are suppositories recommended
- for patients who are unable to make use of oral route of drug administration (eg. unconscious, severe nausea, post op)
- drugs that are less suited for oral administration
disadvantages of suppositories for drug delivery
- strong feeling of aversion
- suppositories that can leak
- slow onset (~30min) and incomplete drug absorption
- considerable intersubject and intrasubject variation in drug absorption
- development of proctitis (infammation of tissue lining rectum)
desirable properties of suppository base
- can be moulded by pouring or compression
- stable if heated above MP
- does not adhere to mould
- release drug at desired rate
- keeps 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
types of bases
oleaginous, water soluble/miscible, emulsifying
oleaginous bases
oily/fatty bases
eg: theobroma oil, hydrogenated fatty acids of vegetable oils, monoglycerides of high MW fatty acids
theobroma oil
aka cocoa butter, composed of triglycerides of mainly oleic stearic and palmitic acid, occurs in three crystalline forms-
- alpha (unstable, MP 22-24)
- beta (stable, MP 24-36), note the use of low heat (40-50 degree) and slow cooling are crucial for direct recrystallisation to beta-crystals
- gamma (unstable, MP 18)
disadvantage of theobroma oil base
- melting provess must be carefully monitored
- theobroma oil tends to stick to the sides of the mould
- theobroma oil tends to soften in tropical climate and when substances such as colatile oils, phenol or chloral hydrate are added
- theobroma oil is difficult to administer as it will melt on finger tip
- theobroma oil tends to leak out of orifice
water soluble/miscible bases
does not melt but dissolve slowly in biological fluid, and are commonly prepared from glycerinated gelatin or polyethylene glycols
what does glycerinated gelatin contains
gelatin- for hardness
glycerin- for hydrophilicity (allow base to attract water)
what are the two types of gelatin
- pharmagel A- cationic and incompatible with anionic compounds
- pharmagel B- anionic and incompatible with cationinc compounds
advantage of glycerinated gelatin base
- more prolonged drug release; commonly used in pessaries
2. more easily inserted; suitable for urethral administration
disadvantage of glycerinated gelatin base
- hygroscopic; dehydrating effect on mucous membrane
2. support growth of mould (need to be hygienically stored)
what are carbowaxes
Polyethylene glycols
what are PEG general formula
HOCH2 (CH2OCH2)n CH2OH,
common MWL 200, 400, 600, 1000, 1500, 1540, 3350, 4000, 6000
advantages of PEG bases
due to higher MP: 1. convenient storage 2. easy insertion 3. no leakage from orifice due to varying solubilities: 4. control of drug release
disadvantage of PEG bases
- incompatible with phenols
2. hygroscopic
emulsifying bases
composed of triglycerides with one or more emulsifying agents
witepsol
hydrogenated triglycerides of lauric acid with added monoglycerides
massupol
glyceryl esters, chiefly lauric acid, with added glyceryl monostearate
advanatage of emulsifying bases
- not adversely affected by overheating
- solidify rapidly at RTP
- do not adhere to mould
- non-irritating
hot process of preparation of suppositories
- fusion or melt moulding, unsuitable for thermolabile drug
- more commonly employed than cold process
- base is melted over hot water-bath, and drug is dissolved or dispersed in the molten base
- molten mixture is poured into lubricated mould and allowed to set in the cold
- suppositories formed are removed from the metal moulds or supplied in the disposable moulds
cold process of preparation of suppositories
- hand moulding (slow process for small scale production; base kneaded throughly with drug) or compression moulding (partially automated and relatively faster than hand moulding)
- does not employ heat and is suitable for thermolabile drugs
types of packaging of suppositories
- partitioned boxes
- screw-capped glass/ plastic containers
- aluminum foil wrappings
- disposable plastic moulds
what packaging is suitable for suppositories that have tendency to fuse contact
partitioning boxes or disposable mould
storage for each types of suppositories
- theobroma oil (<30 degree, in the fridge)
- glycerinated gelatin (<35 degree, dont need be in the fridge but just within suitable temp)
- PEG (can store at RTP due to higher MP)
potential storage problems for different types of suppositories
- theobroma oil: bloom effect- white powdery deposit due to effect of temperature fluctuation that causes unstable forms of theobroma oil to emerge on surface)
- fat base: elevated MP
factors of evaluation of suppositories
- appearance
- uniformity of weight*
- uniformity of drug content
- disintegration time*
- drug release profile
- mechanical strength
- melting behaviour
appearance of suppositories
- color, surface condition, shape, uniformity of mix
- sliced lengthwise for examination
uniformity of weight
- BP method: take 20 suppositories at random from batch, weight individually, then calculate their ave weight
- acceptance criteria: <=2 deviate from average weight by >5% AND none deviates by >10%
uniformity of drug content
drug is extracted from base and assayed using appropriate methods; only for suppositories that need to comply w this test
disintegration time test
disintegration affect rate of drug release, test determines whether suppositories disintegrate or soften within a prescribed time when placed in a liquid medium under prescribed experimental conditions; carried out on 3 separate suppositories
results of disintegration test
complete if any one:
- suppository is completely dissolved
- suppository has dispersed into its component parts
- suppository has become soft and mass has no solid core offering resistance to pressure with a glass rod
acceptance criteria of disintegration test
fat base: disintegration time <=30min
water soluble: disintegration time <=60min
note: all 3 suppositories tested must pass
drug release profile
obtained by determining the amount of drug release from the suppository to the external medium over time
dissolution test
basket method paddle method (dialysis membrane)
mechanical strength
suppository should be strong enough to withstand the rigours of normal handling
melting behaviour
- softening temperature: temp at which deformation occurs; indicates ease of insertion and physical stability of suppository during handling
- liquefaction temperature: temp at which melting occurs, affect drug release, only needed for oleaginous base
physiochemical factors of suppositories that affect release of bioavailability of drugs
- chemical composition of base
- lower viscosity of base more bioavailable due (increase effective area of drug absorption)
- increase interaction bet drug and base (increase absorption)
- increase partition coefficient of drug btw base and rectal tissue (reduce tendency of leaving the base)
- increase drug particle size (increase extend of spreading)
- charge on drug molecule
- lipid solubility of drug (lipid solubility to permeate membrane)
- surface property of drug (greater wettability increases absorption)
- increase amt of drug (increase absorption)
- effect of supp on rectal tissue
important properties of base
- stability
- compatibility with other components
- viscosity
- rate of drug release
- temperature range btw melting and solidification
- volume of contraction
- brittleness
- hygroscopicity
important properties of drug
- solubility
- particle size
- surface property
- amount in base
- displacement value
displacement value
number of parts by weight of a drug which displace one part by weight of base
