Transcript suppositories

Introduction
• Suppositions and pessasies
• Are semisolid dosage forms meant for
Insertion into body cavities.
• Formulated to melt at body temperature.
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Merits :
• Used to treat local conditions such as hemorrhoids in
rectum, infections in vagina
• Useful in infants, debilitated patients, nausea, vomiting,
incapability of swallowing and GIT disturbances
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• For prolonged action of drugs
• Faster onset & action than oral administration
• Degradation at gastric PH is avoided
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Demerits :
• Should be stored at freezed conditions
• Inconvenient to patients.
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FIG.NO.1: SHAPES AND SIZES OF
SUPPOSITORIES
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Types of suppositories
Rectal suppositories :
• For introduction into the rectum
• For systemic action
Vaginal suppositories :
• Meant for introduction into vagina med for local action
Nasal suppositories :
• Meant for introduction into the nasal cavity
• Also known as nasal bougies
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Urethral suppositories :
• For introduction into urethra
Ear cones :
• For introduction into the ear
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New trends of suppositories :
1. Tablet suppositories
Prepared by compression
2. Layered suppositories
Contain different drugs in different layers
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3. Capsule suppositions
Soft gelatin capsules & different shapes
and sizes are used
4. Coated suppositions
Coated by dipping in solution of coated
materials
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5. Disposable suppositions:
Suppository material is poured into the
disposable moulds and cooled.
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Suppository Bases
• Suppository base exert influence on the action of
the drug
Ideal properties of base are :
• Should melt at body temperature
• Should keep its shape
• Should release the medicament readily
• Should be non-t0xic,non-irritant to the mucous membrane
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•
Should be stable an storage
•
Should be compatible with large number of drugs
•
Should be stable it heated above its melting point
•
Should be easily moulded
•
Should have wetting and emulsifying properties.
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Types & Suppositories bases
• Oleaginous bases
• Water soluble bases
• Water miscible bases
• Emulsifying bases
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Oleaginous Bases
• Theobroma oil
• Yellowish white solid
• Obtained from crushed and roasted seeds of
theobroma cocoa
• Known as coca butter
• M.P-30-350c
• Mixture & glyceryl esters of Stearic acid
Oleic acid and Palmitic acid
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Disadvantages
•
Shows phenomena of polymorphism
•
When melted and cooled get solidified into different
crystalline forms depending upon melting temperature
rate & cooling ,size & the mass.
•
Becomes rancid and melts in warm weather
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•
Sticks to the sides of the mould
•
Leakage from body cavities
•
Immiscible with body fluids
•
Liquefy when combined with drugs like chloral hydrate
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Emulsified Theobrama oil
Used when large quantities of aqueous solutions
are to be incorporated
•
5%
•
10% lanette wax
•
2-3% cetyl alcohol
•
4%
•
12% spermaceti
glycerol momostearate
bees wax
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Hydrogenated oils
Obtained by hydrogenation of vegetable oils like
• Arachis oil
• Cotton seed oil
• Coconut oil
• Palm oil
• Used as a substitute for theobroma oil
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These are
• Resistant to oxidation
• Lubrication & mould is not required
• Over heating does not affect the solidifying point
• Produce colorless, odour less elegant suppositories
• Good emulsifying and water capacities
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Disadvantages :
• Become brittle on rapid cooling
• More fluid than theobroma – when melted
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Aqueous bases are water soluble and water miscible bases
They are three types :
•
Glycero-gelation bases
•
Macrogol bases
•
Soap glycerin bases
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Glycerogelatin Bases
• Mixture of glycerol and water with gelatin
• Suitable for suppositories and pessaries
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• Glycerogelation base B.P. contains 14%w/w
gelatin, 70% glycerol and rest water
• USP. base contains 20%w/w gelatin
70% glycerol and rest water
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Advantages
• Dissolves in body secretions
• Provides prolonged release slower to soften, mix with
physiologic fluids
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Disadvantages
•
Difficult to prepare and handle
•
Solution depends an the content and quality of gelatin
•
Gelatin is gyroscopic, requires cold storage
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•
Gelatin is incompatible with drugs like tannic acid,
Gallic acid and ferric chloride
•
More changes of bacterial and mould growth
preservative is required
•
Has physiological action as laxative
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Soap – glycerin suppositories
• Gelatin is replaced with sodium stearate
• Soap helps in the evacuation action of glycerin
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Disadvantages
•
Hygroscopic
•
Must be protected from atmosphere
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Polyethylene glycols : (PEG)
• PEG`s are commonly known as carbowaxes or
polyglycols or macrogols
• Physical character changes according to molecular
weight
• Macrogols < 1000 are liquids
• Macrogols > 1000 are solids
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Advantages
• Chemically stable
• Non – irritant
• Do not allow bacterial or mould growth
• Physiologically inert
• Provide prolonged action
• Do not stick to the mould
• Have smooth and clean appearance
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Disadvantages
• Hygroscopic – require special storage condition
• Incompatible with drugs like tannins, phenols
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Emulsifying bases
• Synthetic bases
Witepsol :
• Consists of triglycerides of saturated vegetable acid
and partial Estes
• Small amount of bees wax is added in hot climates
• Suppositories should be cooled quickly mould should
be lubricated
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Massa Esterinum
• Mixture of mono, di and triglycerides of saturated fatty
acids also known as adeps solidus
• White, brittle, odorless
• Tasteless solid
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• M .p -33.5 to 35.5
• Available in various grades
• Grade B is commonly used in dispensing
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Massuppol
• Consists of glyceryl esters of Lauric acid
• Small amount of glycerol monostearate to improve water
absorbing capacity
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Advantages
• Does not alter the physical characteristics
• Solidify rapidly, Non-irritant
• Lubrication is not required
• Can absorb fairly large amount of water on aqueous
liquid
• White, odorless,clean and attractive
• Less liable to rancidity
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Disadvantages
• Should not be cooled rapidly
• Not very viscous on melting
• Medicaments settle down rapidly
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Suppositories are prepared by

Rolling method

Hot process or fusion method

Cold compression
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Rolling Method
Ancient Method
 Base is rolled into desired shapes with hand
 Method is not used now a days
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Hot Process Or Fusion Method
 Used for dispensing purposes
 Base is melted and medicament is incorporated
 Filled in lubricated mould
 Cooled and removed
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Suppository Mould
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Suppository moulder
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Moulds
In dispensing
 of various types and sizes are available
 Suppository mould having 6-12 cavities with desired shape
and size
 Made of stainless steel, nickel, copper ,alloy , brass
aluminum and plastic
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Cleaning
 Mould is opened longitudinally by removing screws
 Cleaned by immersing in hot water containing detergent
 Rinsed thoroughly
 Wiped gently with soft cloth , then dried
 Lubricated if necessary
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Lubrication Of Mould


Essential for cocoa bitter base glycerol gelatin base
Lubricant used for Cocoa butter





Soft soap
Glycerin
Alcohol 90%
Glycero- gelatin
 Liquid paraffin or arachis oil
Emulsifying base
 No lubricant is used
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 Lubricant is applied with a brush or gauze swab
 Do not use cotton (fibers detach easily)
 Drain excessive lubricant by keeping the mould in
inverted position on ice
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Calibration of the mould
 Size remains the same, Weight varies
 Densities of bases and medicaments are different
 Calibrated for individual base and medicament
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Displacement Values
 To prepare suppository of uniform and accurate weight
 Must be made for the change in density of the mass due
to added medicaments
 So displacement value is used which is defined as
 “The quantity of the drug which displaces one
part of the base”
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Displacement value of a given medicament may
be determined as follows
 Find out the weight of 5 suppositories

containing theobroma oil = a g

containing says 20% medicament = b g
 Calculate the amount of
 theobroma oil present in medicated suppositories
= (80/100)*b = c g
 medicament present in medicated suppositories
=(20/100)*b = d g
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
Calculate the amount of theobroma oil displaced by
d g of medicament = (a-c) g

Displacement value of the medicament ( amount of
drug displaces 1 g of base
=(d/ (a-c)
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 weight of 5 suppositories


containing theobroma oil = 5 g

containing says 40% medicament = 5.5 g
Calculate the amount of
 theobroma oil present in medicated suppositories
= (80/100)*5.5 = 4.4 g
 medicament present in medicated suppositories
= (20/100)*5.5 = 1.1 g
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 the amount of theobroma oil displaced by
1.1 g of medicament = (5 – 4.4) = 0.6 g

0.6 g theobroma oil is displaced by 1.1 g medicament
 1 g theobroma oil will be displaced by
=(1.1/ 0.6) = 1.8 g
 Displacement value of medicament= 1.8 g
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Cold Compression Method
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Method
•
Avoids heat and stirring
•
Useful for thermolabile drugs and insoluble drugs
•
Not suitable for bases where melting is required
Steps involved are
•
Cocoa butter is grated
•
Mass is prepared by mixing powdered drug with
equal quantity of grated Cocoa butter
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• Then add remaining amount of grated Cocoa butter
• Allowance is made for unavoidable wastage during
the preparation
• Compression of the prepared mass is done on
hand or power operated compression machines
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Cold compression machine for suppositories
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• Prepared mass C is placed in a cylinder A
• Which is forced through the narrow opening D
• by applying pressure to the piston B
• Thus forming suppositories at E
• Pressure is further applied, stop plate F is removed
• The finished suppositories are taken out
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• On large scale manufacturing
• Hydraulically operated cold-compression
machines are used
• Which are cooled by water jackets
• to prevent heat of compression from making
the mass too fluid or
• mass and the compression cylinder of the
machine may be chilled on small scale
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Package and Storage
• Packed in shallow partitioned card board
boxes in upright position
• Do not allow them to come in contact with
each other
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• Commercial suppositories are packed separately in
aluminum foil or P V Cc polyethylene strip
• Glycero-gelation suppositories are packed in tightly
closed screw capped glass container
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• Suppositories are directly moulded in to primary
packing made of plastic material or aluminum foil
• Mould are sealed
• Excess is trimmed off
• Finally packed in cartons
• Stored in cold place to retain the shape
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Labeling
• Labeled with instructions “store in a cool place”
• Warning
• “not to be taken orally”
Or
• For rectal use only
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Rx
Alum
300 mg
Theobroma oil q.s
Fiat: Suppositories mitte tales quarta
Sig: Onus omni nocte utendum
Displacement value of alum is 2.0
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Procedure
• Considering the wastage calculate for 5
suppositories instead of 4
• Melt the calculated quantity of theobroma oil
in a dish
• Pour half of melted theobroma oil on
powdered alum placed on a tile
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• Mix thoroughly
• Transfer to dish
• Warm if necessary
• Pour into the cavities of lubricated mould
• Keep on ice
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• Fill five cavities to over flowing
• Allow mass to solidify
• Trim off excess of the mass
• Remove the suppositories
• Warm in wax paper
•
Pack in partitioned cardboard boxes
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Evaluation of suppositories
• Every batch of suppositories manufactured
• Must be tested to ensure that required standards
are met
• Each suppository
• Must be visually examined for general appearance
• Suppository containing medicament in suspended form
is sliced longitudinally to determine uniform distribution
• Assays must be carried out
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Tests performed
•
Uniformly of weight test
•
Melting range test
•
Liquefaction or softening time test
•
Breaking test
•
Disintegration/ dissolution test
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Uniformity of weight test
• Weight 20 suppositories
• Average weight is calculated
• Each suppository is weighted individually
• Deviation should not be more than 5%
• Two should not deviate by more than 7.5%
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Melting Range Test
• Also known as macromelting range test
• Test is performed for suppositories containing fatty base
only
• To check physical and absorption characteristics
• Time taken for entire suppository to melt is measured
•
USP tablet disintegration apparatus is used
•
Suppository is immersed completely in constant
temperature i.e., 37o C water bath
• Time taken for melting is noted
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Liquefaction Or Softening Time Test
• Performed on rectal suppositories
• A glass rod is placed on the suppository held
in U –tube of the apparatus immersed in water
bath
• Time take for the rod to pass through the
suppository is recorded as softening time
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Breaking test
• Or fragility test
• To determine tensile strength
• Can withstand the hazards of packing, transporting
normal handling
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Disintegration / Dissolution Test
• For water soluble bases
• Disintegration / dissolution apparatus USP are
used
• Test media is modified accordingly
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Factor Affecting Drug Absorption From
Rectal Suppositories
•
Release of drug and absorption depends
•
Physiologic factors
•
Physico-chemical characteristics of
• The drug
• The base and adjuvant
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Physiologic Factors
• Number of drugs cannot be administered orally
• Get destroyed in the stomach
• Therapeutic activity is modified or reduced by
liver
• 50-70% drugs administered through rectum
• are absorbed directly into blood circulation
• Bypassing the liver
• PH of rectal fluids plays an important role
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• Absorption of acidic drug increases and basic drug
decreased when ph decreased
• Anorectal membrane also plays a role in absorption of
drugs
• Membrane is covered with mucous which acts as
mechanical barrier for free passage of drug molecules
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Physico-Chemical characteristics of the
drug
• Fat soluble release in slow
• Water soluble drug is faster
• Distribution depends on
• Nature of the drug
• Surfactants
• Physiological condition of colon and
• Chemical nature of the solids & liquids present in it
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Physico -Chemical characteristics of base
and adjuvants
• Absorption rate is faster from oily bases with low
melting point
• Adjuvant affect dissolution of the drug
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