Suppositories Flashcards
Definition of suppositories
Solid dosage forms intended for insertion into body orrifices (other than oral cavity) where they melt/soften/dissolve & exert local or systemic effects
- Comes in various size & shapes
- Diff names according to which body orrifice they are inserted in
Suppository: Rectal administration (1/2g)
Pessary: Vaginal (4/8g)
Urethral bougie: Pencil-shaped for urethral
Nasal bougie: Nasal
Ear cone
Applications of suppositories
1) Carry drug for action at site of placement
2) Carry drug for systemic action
- H/w primarily used for constipation & haemorrhoids
Advantages of suppositories
KIV
Disadvantages of suppositories
- Strong feeling of aversion
- Suppositories can leak
- Slow onset (~30min) & incomplete drug absorption
- Considerable intersubject & intrasubject variation in drug absorption
- Development of proctitis
(Inflmm of tissue lining in rectal wall)
Desirable properties
- Can be moulded by pouring/compression
- Stable if heated above melting point
- Does not adhere to mould
- Release drug @ desired rate
- Keeps shape when handled & easy to insert
- Does not leak out of orrifice into which it is inserted
- Stable during storage
- Non-toxic & non-irritating
- Compatible with drug
List types of suppositories bases
1) Oleaginous bases
2) H2O-soluble/miscible bases
3) Emulsifying bases
Oleaginous bases (Use, Examples, Advantages, Disadvantages)
Also known as oily/fatty bases
Eg. Theobroma oil, Hydrogenated fatty acids of vegetable oils, Monoglycerides of high MW fatty acids
Theobroma oils (aka cocoa butter)
- Composed of triglycerides of mainly oleic, stearic & palmitic acids
- Occurs in 3 crystalline forms
- -> Beta-form: Stable; MP of 34-34 degrees
- -> When heated >60C, will form Alpha-form, take several days to convert to Beta-form
- -> Use low heat (40-50C) & slow cooling for direct recrystallization to Beta-crystals
Disadvantages of Theobroma oils bases:
- Melting process needs to be carefully monitored
- Tends to stick to side of mould
- Tends to soften in tropical climates/ when substances like volatile oils, phenol or chloral hydrate are added
- More difficult to administer as theobroma oil melts on the fingerprint
- Tends to leak out of orifice
Alternatives: Fattibase
H2O-Soluble/Miscible bases (Use, Examples, Advantages, Disadvantages)
- Do not melt but DISSOLVE SLOWLY in the biological fluids
- > Commonly prepared from glycerinated glycerin/polyethylene glycols
Glycerinated Glycerin (Gelatin + Glycerin + H2O)
Gelatin -> Impart hardness to base
Glycerin -> Impart hydrophilicity to base
Comes in 2 types (Important to use correct one):
i) Pharmagel A: Cationic (Incompatible w Anionic cmpds)
ii) Pharmagel B: Anionic (Incompatible w Cationic cmpds)
Polyethylene Glycols (aka Carbowaxes): - A combi of PEGs is often employed to obtain a base of desired hardness, melting pt & H2O-solubility
Advantages of PEG bases:
- Can formulate bases with higher MP (Convenient storage, easy insertion, no leakage from orifice)
- Can formulate bases with varying solubilities for controlled release of drug (Depending on combi of PEGs used)
Disadvantages of PEG bases:
- Incompatible with phenols
- Hygroscopic (Tend to absorb moisture from air)
Emulsifying bases (Use, Examples, Advantages, Disadvantages)
Composed of triglycerides with 1/more emulsifying agents:
Eg. Witepsol: Hydrogenated triglycerides of lauric acid with added monoglycerides
Massupol: Glyceryl esters, chiefly lauric acid with added glyceryl monostearate
Advantages:
- Not adversely affected by overheating
- Solidify rapidly @ rtp
- Do not adhere to mould
- Non-irritating
Disadvantages:
- Slow drug release (even slower than PEG)
- Rectal fluid 1-3mL, very small vol for suppository to dissolve in
How to prepare suppositories?
1) Hot process
- Base is melted over a hot-H2O bath & drug is dissolved/dispersed in the molten base
- Molten mixture is poured into lubricated mould & allowed to set in the cold
- Suppositories are removed from the metal moulds/supplied in the disposable moulds
- -> Condition of metal mould is impt
2) Cold process
i) Hand moulding
- Slow process suitable for small scale production only
- Base is thoroughly kneaded with drug, rolled into a thin cylinder of uniform diameter & cut into individual pieces which are hand moulded to desired shape
ii) Compression moulding
- Partially automated
- -> Possible entrapment of air in mould
Packaging of suppositories
Types of packing:
- Partitioned boxes
- Screw-capped glass/plastic containers
- Aluminium foil wrappings
- Disposable plastic moulds
Store suppositories in cool, dry place:
- Theobroma oil (<30C)
- Glycerinated glycerin (<35C)
Generally stable for ~2years
–> Potential problems: Theobroma oil may “bloom” (form white powdery deposits, though can still be used), Fat base (Elevated MP)
Evaluation of suppositories
1) Appearance
- External: Colour, surface condition, shape, uniformity of mix
- Internal: Sliced lengthwise for examination of internal appearance
2) *Uniformity of weight => Reflects uniformity of drug content
How: Take 20 suppositories @ random from batch,
weigh indv, calc avergae weight
- Not > than 2 can deviate from average by > 5% AND none to deviate by > 10%
- Note: NOT required for moulded suppositories that required to be tested for uniformity of drug content
3) Uniformity of drug content (don’t need for wt then)
- Only for specific suppositories
- Drug is extracted from base & assayed using appropriate methods
4) *Disintegration time
- Affects rate of drug release
- Suppositories taken @ random & placed in a liquid medium under prescribed experimental conditions -> Disintegration test determines whether suppositories disintegrate/soften within a prescribed time
Disintegration test:
- Carried out on 3 suppositories separately
- Apparatus put into vessel with at least ~4litres of H20 (36-37C) & fitted with a slow stirrer
- Apparatus inverted every 10min
Disintegration complete when either…
i) Suppository completely dissolved ii) Dispersed into its component parts iii) Has b/c soft & the mass has no solid core offering resistance to pressure with glass rod
Acceptance criteria (For ALL 3) Fat-based: Disintegration time <= 30min H2O-based: Disintegration time <= 60min
5) Drug-release profile (don’t need disintegration)
- Determining amnt of drug released from suppository to external medium over time
- Vessel contains 900mL dissolution medium ~37C with buffer pH of ~7-8 to stimulate rectal pH
Eg. of dissolution tests:
1) Basket method
2) Paddle method using a dialysis membrane
6) Mechanical strength (Eg.Tablet crushing strength tester)
- Suppository should be hard enough to withstand the rigours of normal handling
7) Melting behaviour (For oleaginous base)
i) Softening temp (temp where deformation happens)
- Indicates ease of insertion & phy stability
ii) Liquefaction temp (temp at which suppository melts)
- Affects drug release
Which are BP requirements for evaluation of suppositories
1) Uniformity of weight
2) Disintegration time
Physicochemical factors of suppositories that affect the release & bioavailability of drugs
1) Chemical composition of base
- Oleaginous: Fastest; Emulsifying: Slowest
2) Viscosity of base (Affects extent of spreading, affects SA)
3) Interaction between base & drug
4) Partition coeff of drug between base & rectal fluid
- Increase, decreased tendency of drug release, decrease amnt of drug avail for absorption
5) Drug particle size
- Increase size, decreased dissolution rate, decreased rate of drug absorption
6) Charges of drug molecules
- Rectal fluid prefer > lipophilic molecules, more difficult if charge
7) Lipid solubility of drug
8) Surface property of drug
- Increased wettability, increased dissolution
9) Amount of drug
- Increased [drug], increased drug diffusion & absorption
10) Any effect of suppository on rectal tissue
- May cause expulsion of suppository
Chain of events when suppository is inserted into the rectum, leading to the bioavailability of the drug
When inserted into rectum, base melts & spreads on mucous lining –> Sedimentation –> Wetting –> Dissolution
