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Dosage - Chapter 12

Dosage - Chapter 12

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Published by Kim Manlangit

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Published by: Kim Manlangit on Sep 12, 2010
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Name:
Pharmaceutical Dosage
Chapter 12: Suppositories and Inserts
Suppositories

y
From the Latin word, supponere meaning ³to place under´
y
Semisolid dosage forms for insertion into the body orifices
y
Melt, soften, or dissolve and exert localized or systemic
effects
y
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
y
Taken when a drug:

Cannot be tolerated: cause to vomit orally
Cannot be swallowed: cause choking
Decomposed or inactivated by pH or enzymes in

theGIT
Destroyed in the liver (oral administration)
Disadvantages of Suppositories
y
Inconvenient, absorption is irregular and difficult to predict
Local Action
y
Suppository base melts distributing the medicaments to the
tissue of the region
y
Rectal suppository: relieves constipation or pain, irritation,
itching and inflammation like hemorrhoids and other
anorectal conditions
y
Glycerin suppositories: laxative action by irritating the
mucous membranes through its dehydrating action
y
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)

y
Urethral suppository: antibacterial and local anesthetic
prepared to urethral examination, contraceptive agents
Systemic action
y
Mucous membrane of the rectum and vagina: permits
absorption of many soluble drugs
Examples ofRectal Suppository for Systemic Effects
y
Aminophylline and theophylline: relief of asthma
y
Prochlorperazine and chlorpromazine: nausea and vomiting
and as tranquilizers
y
Chloral hydrate: sedative and hypnotic
y
Oxymorphone HCl: narcotic analgesic
y
Ergotamine tartrate: migraine syndrome
y
Aspirin: analgesic and antipyretic
Advantages overOralTherapy of theRectalRoute of Administration
for Achieving Systemic Effects
y
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
y
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
SomeFactors of Drug Absorption fromRectal Suppositories
y
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
y
Physicochemical factors of the drug
Dr u g
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
y
Preferable to incorporate ionized form (salt form) to
maximize bioavailability
PhysicochemicalFactors of SuppositoryBase
y
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.

y
Particle size
Influences released and dissolved amount in
absorption
The smaller, the readily the dissolution and
greater chance for rapid absorption.
SuppositoryBase
y
Capable of melting, softening, or dissolving to release its
drug components for absorption
Undesirable Characteristics of a Base
y
Interacts with the drug, inhibiting its release: drug
absorption prevented or delayed
y

Irritating to the mucous membrane of the rectum, initiating a colonic response and prompt to a bowel movement: negating drug release and absorption

2
Classification of SuppositoryBase
y
Fatty or oleaginous bases
Frequently employed since cocoa butter
(triglyceride) is a member of other triglycerides
Wecobee bases: derived from coconut
oil
Witepsol bases: saturated fatty acids
C12 to C18
Other fatty oleaginous materials
Hydrogenated fatty acids of vegetable
oils (palm kernel oil and cottonseed oil)
Fat based compounds containing compounds of

glycerin HMW fatty acids: palmitic and stearic acids (glyceryl monostearate and glyceryl monopalmitate)

y
Water-soluble or water-miscible bases
Main members of this group are bases of:
Glycerinated gelatin
o
Have tendency to absorb
moisture
due
to
the
hygroscopic
nature
of
glycerin
causing
the
following effect:
May lose their
shape
and
consistency
May

lose dehydrating effect and be irritating to the tissues upon insertion

o
Remedy
Water
present
minimizes
these
effects
Su p p os it or y
is
moistened
with
water
prior
to
insertion

(reduce tendency of base to draw water from the

mucous
membranes
and
irritates tissue)
Bases of polyethylene glycols
o

Polymers of ethylene oxide and water prepared to various chain lengths, molecular weight ranges of 200, 400, 600, 1000, 1500, 1540,3350, 4000, 6000, and 8000 and physical states

Do not melt at body
temperature

and dissolve slowly in the body¶s fluids

Slower release of
medication
from
the
base
once
inserted
Pe r mit s

the convenient storage without need of refrigeration

and without danger of softening

excessively
in
warm weather
Do not leak from
the orifice
Dipped in water

before use to avoid irritation of mucous membrane

y
Miscellaneous bases
Mixture of oleaginous and water-miscible
materials
Mixture of many fatty acids with emulsifying
agents capable of forming without emulsion: also
referred as ³hydrophilic´ suppository base
A soap as a base like glycerin suppositories
which have sodium stearate
CocoaButter
y
A triglyceride (glycerin + one or different fatty acids)
primarily of oleopalmitostearin and oleodistearin
y
Melts between 30o to 36oC
y
Ideal suppository base, melting just below body
temperature maintaining solidity at room temperature
y
Exhibits marked polymorphism (to exist in several different
crystalline forms, with the triglyceride content)
y

Crystalline form represents a metastable condition ( crystals with lower melting point), slow transition to the more stable  form of crystals (greater stability and high melting point)

y
Slowly and evenly melted on a water bath
Avoid formation of unstable crystalline form
Ensure the retention in the liquid of the more
stable  crystals
y
Lowers the melting point when incorporated: phenol and
chloral hydrate
y
Solidifying agents melted with cocoa butter to compensate
for the softening effect of the added substances
Cetyl esters wax (20%)
Beeswax (4%)
Different Preparations of Suppositories
y
Molding from melt or fusion (commonly employed in small
scale and industrial scale)
y
Cold compression
y
Hand molding or rolling and shaping
y
Compression in a tablet press
Preparation of Suppositories
y
Preparation by molding
Melting of the base preferably in water or stream
bath to avoid local overheating
Incorporating the required medicament: either
emulsified or suspend in it
Pouring the melt into the cooled metal mold
which are usually chrome or nickel plate
Allowing the melt to cool and congeal thoroughly
using refrigerator in a small scale or refrigerated
air on a larger scale
Removing the formed suppositories from the
mold
SuppositoryMolds
y
Made from stainless steel, aluminium, bass or plastic
y
Separated into sections (longitudinally), opened for
cleaning before and after a batch preparation of suppository
y
Scratches should be avoided especially the plastic
Lubricating theMolds
y
Before the melt is poured:
3
Facilitates cleaning and easy removal of the
molded suppository
y
Lubricant used: thin coating mineral oil or expressed
almond oil applied with the finger to the molding surface
y

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)

y
Necessary when glycerinated gelatine suppositories are
prepared
Calibration ofMolds
y
Calibrate each of suppository molds for the suppository
bases to have proper quantity of medicament
y
Suppositories are weighed and the total weight and average
weight of each are recorded
y
Suppositories are carefully melted in a calibrated beaker
(determine the volume of the mold)
y
The volume of the melt is determined for the total number
as well as the average of one suppository
Determination of the Amount ofBaseRequired
y
First method
Total volume needed: volume of the drug
substance
y
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 theMelt
y
Weighed suppository base material is melted (least possible
heat0 over water bath
y
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

y
The pouring must be continuous to prevent µlayering¶
which may lead to a product easily broken on handling
y
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.
y
When suppositories are hard, the mold is removed from the
freezer and dislodged the suppositories from the mold.
y
Generally, little pressure is required to let fall the
suppository of their mold.
Preparation by Compression
y

Prepared by forcing the mixed mass of the suppository base and the medicament into special molds using suppository molding machines

y
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
y
Method is simple
y
Resulting suppository is more elegant that of hand molding
y
Avoid the possibilities of sedimentation of the insoluble
solids in the suppository base
Disadvantages of Preparation by Compression
y
Too slow for large scale operation
y
Triturate in a mortar, then formed in into a ball in the palms
of the hands previously cooled in the ice water
y
A broad bladed spatula or flat board is used to roll it to a
cylinder on a pile tile
y
Cut with a spatula into sections and shaped desired
Compression in aTablet Press
y
Carbon dioxide releasing tablet (compressed rectal
suppository)
Made of dried sodium biphosphate, NaHCO3a nd
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
y
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
y
Using half of a suppository should cut it lengthwise with
clean razor blade
y
Dispensed in paper, foil, or plastic wrappings
y
Removal of wrapper before insertion
Packaging and Storage
y
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)
y
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)
y
More widely used than the vaginal suppositories

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