Name:
Pharmaceutical Dosage
Chapter 12: Suppositories and Inserts
Suppositories
 From the Latin word, supponere meaning “to place under”
 Semisolid dosage forms for insertion into the body orifices
 Melt, soften, or dissolve and exert localized or systemic
effects
 Types
 Rectal suppository
 Cylindrical and tapered at one end
 Bullet-shaped
 1 gram for infants and 2 grams for adult
 Vaginal suppository
 Pessaries
 Globular oviform or conical in shape
 3 to 5 grams in weight
 Urethral suppository
 Bougies
 Pencil-shaped: 4 to 5nm
 For males: weigh 4 grams, 100 to
150mm long
 For females: 2 grams, 60 to 70mm long
Advantages of Suppositories
 Taken when a drug:
 Cannot be tolerated: cause to vomit orally
 Cannot be swallowed: cause choking
 Decomposed or inactivated by pH or enzymes in
the GIT
 Destroyed in the liver (oral administration)
Disadvantages of Suppositories
 Inconvenient, absorption is irregular and difficult to predict
Local Action
 Suppository base melts distributing the medicaments to the
tissue of the region
 Rectal suppository: relieves constipation or pain, irritation,
itching and inflammation like hemorrhoids and other
anorectal conditions
 Glycerin suppositories: laxative action by irritating the
mucous membranes through its dehydrating action
 Vaginal suppository for localized effects: contraceptives
(Nonoxynol 9) and antiseptic in feminine hygiene and
specific agents to combat invading pathogens
(Trichomonas vaginalis, Candida [monilia] albicans,
Hemophilus vaginalis)
 Urethral suppository: antibacterial and local anesthetic
prepared to urethral examination, contraceptive agents
Systemic action
 Mucous membrane of the rectum and vagina: permits
absorption of many soluble drugs
Examples of Rectal Suppository for Systemic Effects
 Aminophylline and theophylline: relief of asthma
 Prochlorperazine and chlorpromazine: nausea and vomiting
and as tranquilizers
 Chloral hydrate: sedative and hypnotic
 Oxymorphone HCl: narcotic analgesic
 Ergotamine tartrate: migraine syndrome
 Aspirin: analgesic and antipyretic
Advantages over Oral Therapy of the Rectal Route of Administration
for Achieving Systemic Effects
 Drugs
 Destroyed or inactivated by the pH or enzymatic
activity of the stomach or intestines need not to
be exposed to these destructive environments
 Destroyed by portal circulation: may bypass the
liver after rectal absorption
 Irritating to the stomach may be given without
causing such irritation
 Route is:
 Convenient for administration of drugs to adult or
pediatric patients who may be unable or
unwilling to swallow medications
 Effective in the treatment of patients with
vomiting episodes
Some Factors of Drug Absorption from Rectal Suppositories
 Physiologic factors
 Colonic contents
 Drug have greater absorption in the
absence of fecal matter
 Other conditions (diarrhea, colonic
obstruction due to tumor growths and
tissue dehydration) influence rate and
degree of drug absorption
 Circulation route
 Drugs rectally absorbed: bypass the
portal circulation, thus enable drugs
(destroyed in the liver) to exert
systemic effects
 Lymphatic circulation also assists in
the absorption of rectally administered
drug.
 pH and lack of buffering capacity of the rectal
fluids
 Rectal fluids neutral in pH and have no
effective buffer capacity therefore
drugs do not chemically changed
 Physicochemical factors of the drug
 Drug
 Relative solubility of the drug in lipid
and in water
 Particle size of the dispersed drug
 Suppository base
 Ability to melt, soften, and dissolve at
body temperature
 Ability to release the drug substance
 Its hydrophilic or hydrophobic
character
For Systemic Drug Action Using Cocoa Butter Base
 Preferable to incorporate ionized form (salt form) to
maximize bioavailability
Physicochemical Factors of Suppository Base
 Lipid-water solubility
 A lipophilic drug distributed in a fatty
suppository base in low concentration has lesser
tendency to escape to the surrounding aqueous
fluids than a hydrophilic substance in fatty base.
 Particle size
 Influences released and dissolved amount in
absorption
 The smaller, the readily the dissolution and
greater chance for rapid absorption.
Suppository Base
 Capable of melting, softening, or dissolving to release its
drug components for absorption
Undesirable Characteristics of a Base
 Interacts with the drug, inhibiting its release: drug
absorption prevented or delayed
 Irritating to the mucous membrane of the rectum, initiating
a colonic response and prompt to a bowel movement:
negating drug release and absorption
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Classification of Suppository Base excessively in
 Fatty or oleaginous bases warm weather
 Frequently employed since cocoa butter  Do not leak from
(triglyceride) is a member of other triglycerides the orifice
 Wecobee bases: derived from coconut  Dipped in water
oil before use to avoid
 Witepsol bases: saturated fatty acids irritation of mucous
C12 to C18 membrane
 Other fatty oleaginous materials  Miscellaneous bases
 Hydrogenated fatty acids of vegetable  Mixture of oleaginous and water-miscible
oils (palm kernel oil and cottonseed oil) materials
 Fat based compounds containing compounds of  Mixture of many fatty acids with emulsifying
glycerin HMW fatty acids: palmitic and stearic agents capable of forming without emulsion: also
acids (glyceryl monostearate and glyceryl referred as “hydrophilic” suppository base
monopalmitate)  A soap as a base like glycerin suppositories
 Water-soluble or water-miscible bases which have sodium stearate
 Main members of this group are bases of: Cocoa Butter
 Glycerinated gelatin  A triglyceride (glycerin + one or different fatty acids)
o Have tendency to absorb primarily of oleopalmitostearin and oleodistearin
moisture due to the  Melts between 30o to 36oC
hygroscopic nature of  Ideal suppository base, melting just below body
glycerin causing the temperature maintaining solidity at room temperature
following effect:  Exhibits marked polymorphism (to exist in several different
 May lose their crystalline forms, with the triglyceride content)
shape and  Crystalline form represents a metastable condition (α
consistency crystals with lower melting point), slow transition to the
 May lose more stable β form of crystals (greater stability and high
dehydrating effect melting point)
and be irritating to  Slowly and evenly melted on a water bath
the tissues upon  Avoid formation of unstable crystalline form
insertion  Ensure the retention in the liquid of the more
o Remedy stable β crystals
 Water present  Lowers the melting point when incorporated: phenol and
minimizes these chloral hydrate
effects  Solidifying agents melted with cocoa butter to compensate
 Suppository is for the softening effect of the added substances
moistened with  Cetyl esters wax (20%)
water prior to  Beeswax (4%)
insertion (reduce Different Preparations of Suppositories
tendency of base to  Molding from melt or fusion (commonly employed in small
draw water from scale and industrial scale)
the mucous
 Cold compression
membranes and
 Hand molding or rolling and shaping
irritates tissue)
 Bases of polyethylene glycols  Compression in a tablet press
o Polymers of ethylene oxide Preparation of Suppositories
and water prepared to various  Preparation by molding
chain lengths, molecular  Melting of the base preferably in water or stream
weight ranges of 200, 400, bath to avoid local overheating
600, 1000, 1500, 1540, 3350,  Incorporating the required medicament: either
4000, 6000, and 8000 and emulsified or suspend in it
physical states  Pouring the melt into the cooled metal mold
 Do not melt at body which are usually chrome or nickel plate
temperature and  Allowing the melt to cool and congeal thoroughly
dissolve slowly in using refrigerator in a small scale or refrigerated
the body’s fluids air on a larger scale
 Slower release of  Removing the formed suppositories from the
medication from mold
the base once Suppository Molds
inserted  Made from stainless steel, aluminium, bass or plastic
 Permits the  Separated into sections (longitudinally), opened for
convenient storage cleaning before and after a batch preparation of suppository
without need of  Scratches should be avoided especially the plastic
refrigeration and Lubricating the Molds
without danger of  Before the melt is poured:
softening

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  Facilitates cleaning and easy removal of the
molded suppository
 Lubricant used: thin coating mineral oil or expressed
almond oil applied with the finger to the molding surface
 Seldom necessary when the suppository base is cocoa
butter or PEG (contract sufficiently on cooling within the
mold to separate from the inner surfaces and allow easy
removal)
 Necessary when glycerinated gelatine suppositories are
prepared
Calibration of Molds
 Calibrate each of suppository molds for the suppository
bases to have proper quantity of medicament
 Suppositories are weighed and the total weight and average
weight of each are recorded
 Suppositories are carefully melted in a calibrated beaker
(determine the volume of the mold)
 The volume of the melt is determined for the total number
as well as the average of one suppository
Determination of the Amount of Base Required
 First method
 Total volume needed: volume of the drug
substance
 Second method
 Requires the following steps:
 Weigh the active ingredient for the
preparation of a single suppository
 Dissolve or mix it with a portion of
melted base insufficient to fill one
cavity of the mold
 Place the mixture to the mold
 Add additional melted base to the
cavity to completely fill the mold
 Remove the suppository from the mold
and weigh
 Total weight of the suppository:
 Weight of the ingredient =
amount of the base needed X
number of suppositories to
make = total base needed
Preparing and Pouring of the Melt
 Weighed suppository base material is melted (least possible
heat0 over water bath
 Medicinal substance incorporated into a portion of the
melted base by mixing on a glass or porcelain tile with
spatula, stir and allowed to cool almost to its congealing
point
 The pouring must be continuous to prevent ‘layering’
which may lead to a product easily broken on handling
 When solidified: the excess material is scraped off the top
of the mold with spatula. The mold is placed in the freezer
to hasten hardening of the suppository.
 When suppositories are hard, the mold is removed from the
freezer and dislodged the suppositories from the mold.
 Generally, little pressure is required to let fall the
suppository of their mold.
Preparation by Compression
 Prepared by forcing the mixed mass of the suppository base
and the medicament into special molds using suppository
molding machines
 On a small scale a mortar is heated in warm water before
use and then dried, the softening of the base and the mixing
process are greatly facilitated forming a paste-like
consistency
 Suppository mass is placed in the cylinder
 Pressure is applied from one end (by turning
wheel) and the mass is forced out at the other end
 A movable end plate at the back of the die is
removed (die is filled with mass)
 Additional pressure is applied to the mass in the
cylinder
 Formed suppositories are ejected
Advantages of Preparation by Compression
 Method is simple
 Resulting suppository is more elegant that of hand molding
 Avoid the possibilities of sedimentation of the insoluble
solids in the suppository base
Disadvantages of Preparation by Compression
 Too slow for large scale operation
 Triturate in a mortar, then formed in into a ball in the palms
of the hands previously cooled in the ice water
 A broad bladed spatula or flat board is used to roll it to a
cylinder on a pile tile
 Cut with a spatula into sections and shaped desired
Compression in a Tablet Press
 Carbon dioxide releasing tablet (compressed rectal
suppository)
 Made of dried sodium biphosphate, NaHCO3 and
starch
 Dipped or sprayed with a coating of water soluble
PEG to add film for protection of the core for the
aid in insertion into rectum
 Vaginal compressed tablet
 Contains active ingredients and lactose
and/or phosphoric acids for adjusting the
acidity of the vagina to pH 5
Information Patients Need to Know About Suppositories
 Using half of a suppository should cut it lengthwise with
clean razor blade
 Dispensed in paper, foil, or plastic wrappings
 Removal of wrapper before insertion
Packaging and Storage
 Packaging
 Glycerin suppository and glycerinated
gelatin suppository
 Tightly closed containers to prevent
moisture change
 Cocoa butter based suppository
 Individually wrapped or separated in
compartment bases
 Light sensitive drugs
 Individually wrapped in opaque material (metallic foil)
 Storage
 Cocoa butter suppository base
 Below 300°C or 860°F
 In a refrigerator: 2o to 80oC or 68o to
770oF
 Glycerinated gelatin suppository
 Below 350°F
 Controlled room temperature
 20o to 250°C or 68o to 770°F
 PEG suppository base
 Room temperature
 Stored of high humidity
 Absorbs moisture and becomes spongy
 Extreme dryness
 Lose moisture and becomes brittle
Vaginal Inserts (Vaginal Tablets)
 More widely used than the vaginal suppositories
 Easier to manufacture, more stable and less messy
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  Avoid accompanied with a plastic inserter for easy  Oinments, creams, and aerosol forms
placement  Protofoam
 Contain same types of anti-infective and hormonal  Jellies and gels
substances as vaginal suppositories  Contraceptive sponge
 Prepared by tablet compression and formulated with:  Intrauterine progesterone drug delivery system
 Base or filler: lactose  Progestasert
 Disintegrating agent: starch  Powders
 Dispersing agent: PVP  Solutions
 Lubricant: magnesium stearate  Vaginal douches
 Some are capsules of gelatin containing medication to be  Enemas
released intravaginally  Retention and evacuation enemas
 Also used rectally, insertion facilitated by lightly wetting  Suspensions
with water  Barium sulfate suspension
Other Inserts
 Tablet and capsules
 Vaginal tablet and inserts

Table 12.1: Examples of Rectal Suppositories

Type of
Suppository Commercial Product Active Constituent Category and Comments
Effect
Bisacodyl Dulcolax (Ciba) 10 mg Local Cathartic. Base: hydrogenated vegetable oil
Antiemetic; tranquilizer. Base: glycerin, glyceryl
Chlorpromazine Thorazine (SmithKline Beecham) 25, 100 mg Systemic monopalmitate, glyceryl monostearate, hydrogenated fatty
acids of coconut and palm kernel oils
Pruritus ani, inflamed hemorrhoids, other inflammatory
Hydrocortisone Anusol-HC (Warner-Lambert) 25 mg Local
conditions of the anorectum. Base: hydrogenated glycerides
Hydromorphone Dilaudid (Knoll) 3 mg Systemic Analgesic. Base: cocoa butter with silicone dioxide
Mesalamine Canasa (Axcan Scandipharm) 500 mg Local Anti-inflammatory. Base: hard fat
Oxymorphone Numorphan (Endo) 5 mg Systemic Analgesic. Base: Polyethylene glycols 1000 and 3350
Antiemetic. Base: glycerin, monopalmitate, glyceryl
Compazine (SmithKline
Prochlorperazine 2.5, 5, 25 mg Systemic monostearate, hydrogenated fatty acids of coconut and palm
Beecham)
kernel oils
Antihistamine, antiemetic, sedative: used to manage allergic
Promethazine Phenergan (Wyeth-Ayerst) 12.5, 25, 50 mg Systemic conditions; preoperative sedation or nausea and vomiting;
motion sickness. Base: cocoa butter, white wax.

Table 12.2: Examples of Vaginal Suppositories and Tablets

Product Active Ingredients Category and
(Manufacturer) Comments
AVC Suppositories Sulfanilamide 1.05g For Candida albicans
(Novavax) infections
Monistat 7 Miconazole nitrate Antifungal for local
Suppositories 200mg vulvovaginal
(Advanced Care candidiasis
Products) (moniliasis)
Mycelex-G Vaginal Clotrimazole 500mg Vulvovaginal yeast
Tablets (Bayer) (Candida) infections
Semicid Vaginal Nonoxynol-9 100mg Nonsystemic
Contraceptive Inserts reversible birth
(Robins Healthcare) control

Multiple choices: Try it!

Choices:
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 A. Rectal suppository E. Undesirable characteristics of a base
B. Vaginal suppository F. For systemic drug action using cocoa butter base
C. Urethral suppository G. Different preparations of suppositories
D. Local Action H. Suppository molds
E. Systemic action I. First method
F. Tablet and capsules J. Second method
G. Ointments, creams, and aerosol forms
H. Intrauterine progesterone drug delivery system Questions:
I. Solutions
J. Enemas 1. ___ Some factors of drug absorption from rectal
K. Suspensions suppositories
2. ___ Drug has greater absorption in the absence of fecal
Questions: matter
3. ___ Irritating to the mucous membrane of the rectum,
1. ___ Protofoam initiating a colonic response and prompt to a bowel
2. ___ Globular oviform or conical in shape movement: negating drug release and absorption
3. ___ Rectal suppository: relieves constipation or pain, 4. ___ Lymphatic circulation also assists in the absorption of
irritation, itching and inflammation like hemorrhoids and rectally administered drug.
other anorectal conditions 5. ___ Rectal fluids neutral in pH and have no effective buffer
4. ___ For males: weigh 4 grams, 100 to 150mm long capacity therefore drugs do not chemically changed
5. ___ Vaginal tablet and inserts 6. ___ Preferable to incorporate ionized form (salt form) to
6. ___ Cylindrical and tapered at one end maximize bioavailability
7. ___ For females: 2 grams, 60 to 70mm long 7. ___ Cold compression
8. ___ Mucous membrane of the rectum and vagina: permits 8. ___ Made from stainless steel, aluminium, bass or plastic
absorption of many soluble drugs 9. ___ Weigh the active ingredient for the preparation of a
9. ___ Progestasert single suppository
10. ___ Glycerin suppositories: laxative action by irritating the 10. ___ Total volume needed: volume of the drug substance
mucous membranes through its dehydrating action
11. ___ Barium sulfate
12. ___ Retention and evacuation
13. ___ Vaginal douches

Choices:

A. Aminophylline and theophylline

B. Prochlorperazine and chlorpromazine
C. Chloral hydrate
D. Oxymorphone HCl
E. Ergotamine tartrate
F. Aspirin
G. Wecobee bases
H. Witepsol bases
I. Cocoa butter
J. Cocoa butter suppository base
K. Glycerinated gelatin suppository

Questions:

1. ___ Nausea and vomiting and as tranquilizers

2. ___ Relief of asthma
3. ___ Narcotic analgesic
4. ___ Derived from coconut oil
5. ___ Saturated fatty acids C12 to C18
6. ___ Analgesic and antipyretic
7. ___ Migraine syndrome
8. ___ Sedative and hypnotic
9. ___ Melts between 30o to 36oC
10. ___ Below 350°F
11. ___ In a refrigerator: 2o to 80oC or 68o to 770oF

Choices:

A. Colonic contents
B. Circulation route
C. pH and lack of buffering capacity of the rectal fluids
D. Physicochemical factors of the drug