Transcript Suppositories - Fakultas Farmasi UNAND

Compounding
Suppository
Dr. Muslim Suardi, MSi., Apt.
Faculty of Pharmacy University of Andalas
Suppositories


Are medicated, solid bodies of various
sizes & shapes suitable for
introduction into body cavities.
The medicament is incorporated into a
base such as cocoa butter which melts
at body temperature, or into one such
as glycerinated gelatin or PEG which
slowly dissolves in the mucous
secretions.
Action



Local action
Systemic effect
To exert a mechanical effect to
facilitate emptying the lower bowel
Ideal Suppository Base





Nontoxic
Nonirritating
Inert, compatible with medicaments
Easily formed by compression or
molding.
Dissolve or disintegrate in the
presence of mucous secretions or melt
at body temperature to allow for the
release of the medication.
Role of Suppository Base

As with the ointment bases,
suppository base composition plays an
important role in both the rate &
extent of release of medications
Utilize Suppositories


Medicated solid formulations that are
inserted into body cavities.
Made in a variety of shapes & sizes
because they are used in many
different ROA (body cavities).
Rectal


Drugs administered via the rectum are
given for a local effect or to achieve a
systemic effect.
Local effects may include the soothing
of inflamed hemorrhoidal tissues,
promoting laxation, & enemas.
Rectal Administration


To achieve systemic activity is
preferred when the drug is destroyed
in the GIT, if oral administration is not
possible because of vomiting, or the
patient is unconscious or incapable of
swallowing oral formulations.
Has been used to treat a variety
conditions such as asthma, nausea,
motion sickness, anxiety, & bacterial
infections.
Common Rectal
Formulations



Suppositories
Solutions
Ointments
Suppositories




Solid dosage forms that dissolve or
melt when inserted into the rectum.
Manufactured in a variety of shapes.
Rectal suppositories for adults are
tapered at one end & usually weigh
2g.
Infant rectal suppositories usually
weight ±1g or ± 1/2 of adult supp
Major Disadvantages



Rectal absorption of most drugs is
frequently erratic & unpredictable.
Some suppositories "leak" or are
expelled after insertion.
They are not preferred by patients;
they are inconvenient.
Vaginal Administration
Advantages



Generally there is less drug
degradation via this ROA compared to
oral administration
The dose can be retrieved if necessary
There is the potential of long term
drug absorption with various IUDs
Vaginal Administration


Lead to variable absorption since the
vagina is a physiologically &
anatomically dynamic organ that
causes pH & membrane permeability
to change over time.
There is also a tendency of some
dosage forms to be expelled after
insertion into the vagina.
Vaginal Formulations



Include: solutions, powders for
solutions, ointments, creams, aerosol
foams, suppositories, & tablets.
Vaginal suppositories are employed as
contraceptives, feminine hygiene
antiseptics, bacterial antibiotics, or to
restore the vaginal mucosa.
Are inserted high in the vaginal tract
with the aid of a special applicator
Shape


Usually globular, oviform, or coneshaped & weigh between 3-5g
Patients should be instructed to
quickly dip the suppository in water
before insertion.
Because they are generally used at
bedtime & can be messy if the
formulation is an oleaginous base,
patients should wear a sanitary napkin
to protect nightwear & bed linens.
Urethral Suppositories


Not specifically described in the USP
24 either by weight or dimension.
Traditionally, they are cylindrical in
shape (3-6 mm in diameter) & vary in
length according to gender.
Female Urethral
Suppositories



Can be 25-70 mm in length while male
urethral suppositories can be about
50-125mm in length.
The one commercially available
urethral suppository is actually
marketed as a "pellet," & is 1.4 mm in
diameter & 3 or 6 mm in length
depending on strength.
They are unusual & may not be
Inserting Rectal
Suppositories




If possible, go to the toilet & empty
bowels.
Wash hands carefully with soap &
warm water.
Remove any foil or plastic wrapping
Lubricate the tapered end of the
suppository with a small amount of KY® Jelly. If the jelly is not available,
moisten it with a small amount of
Inserting Rectal
Suppositories


Separate buttocks to expose the rectal
area.
Gently but firmly push the suppository
into the rectum until it passes the
sphincter (±1/2-1 inch in infants, & 1
inch in adults.
Inserting Rectal
Suppositories


Close your legs & sit (or lay) still for
±15min. Avoid emptying bowels for at
least 1h (unless the suppository is a
laxative). Avoid excessive movement
or exercise for at least 1h
Wash hands again with soap & warm
water immediately after inserting the
suppository.
Inserting Vaginal
Suppositories





Wash hands with soap & warm water.
Remove any foil or plastic wrapping
Place suppository in applicator.
Hold the applicator by the opposite
end from where the suppository is.
Either lay on your back with your
knees bent, or stand with your feet
spread a few inches apart & your
knees bent.
Inserting Vaginal
Suppositories



Gently insert the applicator into the
vagina as far as it will go comfortably.
Once you are ready, push the inside of
the applicator in & place the
suppository as far back in the vagina
as possible.
Remove the applicator for the vagina.
Wash your hands again with soap &
warm water
Suppository Bases



Suppository bases may be
conveniently classified as according to
their composition & physical
properties:
Oleaginous (fatty) bases
Water soluble or miscible bases
Oleaginous Bases


Include Theobroma Oil & synthetic
triglyceride mixtures.
Theobroma Oil or cocoa butter is
used as a suppository base because, in
large measure, it fulfills the
requirements of an ideal base.
Oleaginous Bases


At ordinary room temp of 15-25°C
(59-77°F), it is a hard, amorphous
solid, but at 30-35°C (86-95°F), i.e., at
body temperature, it melts to a bland,
nonirritating oil.
Thus in warm climates, theobroma oil
suppositories should be refrigerated.
Preparing Suppositories
with Cocoa Butter



2 factors of particular attention:
First, this base must not be heated
above 35°C (95°F) because cocoa
butter is a polymorphic compound & if
overheated will convert to a
metastable structure that melts in the
25-30°C (77-86°F) range.
Finished suppositories would melt at
room temperature & not be usable.
Preparing Suppositories
with Cocoa Butter



The second factor is the change in mp
caused by adding certain drugs to
cocoa butter supp.
E.g: chloral hydrate & phenol tend to
lower the mp.
It may be necessary to add spermaceti
/beeswax to raise the mp of finished
supp back to the desired range.
Synthetic Triglycerides





The newer base. Consist of
hydrogenated vegetable oils.
Advantage over cocoa butter: not
exhibit polymorphism. More expensive
Some of the bases are single entity
formulations.
Some may denote a series of bases.
Bases are varied to give a range of mp
Synthetic Triglycerides


E.g: Fattibase® is a single entity base
that consists of triglycerides from
palm, palm kernel, & coconut oils.
Wecobee® is a series of bases.
Wecobee FS, M, R, & S are all made
from triglycerides of coconut oil.
But FS has a mp range of 39.4 to
40.5°C, M has a range of 33.3 to
36.0°C, R has a range of 33.9 to
Water Soluble/Water
Miscible Bases

Ccontaining glycerinated gelatin or the
PEG polymers.
Glycerinated Gelatin



A useful supp base, particularly for
vaginal supp.
Suitable for use with a wide range of
medicaments including alkaloids, boric
acid, & ZnO.
Glycerinated gelatin supp are
translucent, resilient, gelatinous solids
that tend to dissolve or disperse slowly
in mucous secretions to provide
Supp Made with
Glycerinated Gelatin



Must be kept in well-closed containers
in a cool place since they will absorb &
dissolve in atmospheric moisture.
Intended for extended shelf-life should
have a preservative added, such as
nipagin/nipasol, or a suitable
combination of the two.
To facilitate administration,
glycerinated gelatin supp should be
PEG Polymers


Have received much attention as supp
bases in recent years because they
possess many desirable properties.
Chemically stable, nonirritating,
miscible with water & mucous
secretions, & can be formulated, either
by molding or compression, in a wide
range of hardness & mp. Like
glycerinated gelatin, they do not melt
PEG Polymers

May be used singly as supp bases but,
more commonly, formulas call for
compounds of 2 or more MW mixed in
various proportions as needed to yield
a finished product of satisfactory
hardness & dissolution time.
PEG Polymers

Since the water miscible supp dissolve
in body fluids & need not be
formulated to melt at body
temperature, they can be formulated
with much higher mp & thus may be
safely stored at room temperature.
Methods of Preparation
Suppositories can be
extemporaneously prepared by:
1. Hand Rolling
2. Compression Molding
3. Fusion Molding

1. Hand Rolling



The oldest & simplest method of supp
preparation & may be used when only
a few suppositories are to be prepared
in a cocoa butter base.
It has the advantage of avoiding the
necessity of heating the cocoa butter.
A plastic-like mass is prepared by
triturating grated cocoa butter & active
ingredients in a mortar.
1. Hand Rolling


The mass is formed into a ball in the
palm of the hands, then rolled into a
uniform cylinder with a large spatula
or small flat board on a pill tile.
The cylinder is then cut into the
appropriate number of pieces which
are rolled on one end to produce a
conical shape.
1. Hand Rolling


Effective hand rolling requires
considerable practice & skill.
The suppository "pipe" or cylinder
tends to crack or hollow in the center,
especially when the mass is
insufficiently kneaded & softened.
2. Compression Molding

is a method of preparing
suppositories from a mixed mass of
grated suppository base and
medicaments which is forced into a
special compression mold.
2. Compression Molding


The method requires that the capacity
of the molds first be determined by
compressing a small amount of the
base into the dies & weighing the
finished supp.
When API are added, it is necessary to
omit a portion of the supp base, based
on the density factors of the API.
3. Fusion Molding




Involves first melting the supp base, &
then dispersing or dissolving the drug
in the melted base.
The mixture is removed from the heat
& poured into a supp mold.
When the mixture has congealed, the
supp are removed from the mold.
The fusion method can be used with
all types of supp & must be used with
Suppository Volume



Supp are generally made from solid
ingredients & drugs which are
measured by weight.
When they are mixed, melted, &
poured into supp mold cavities, they
occupy a Vol-the vol of the mold cavity
Since the components are measured
by weight but compounded by
volume, density calculations & mold


When a drug is placed in a suppository
base, it will displace an amount of
base as a function of its density.
If the drug has the same density as
the base, it will displace an equivalent
weight of the base.


If the density of the drug is greater
than that of the base, it will displace a
proportionally smaller weight of the
base.
Density factors for common drugs in
cocoa butter are available in standard
reference texts.

The density factor is used to
determine how much of a base will be
displaced by a drug. The relationship
is:

Eg. ASA has a density factor in cocoa
butter of 1.3. If a supp is to contain
0.3g of ASA, it will replace 0.3g÷1.3 or
0.23g of cocoa butter. If the blank
supp (supp without the drug) weighed
2g, then 2g-0.23g or 1.77 g of cocoa
butter will be needed for each supp, &
the supp will weigh 1.77g+0.3g=2.07g

So if a pharmacist was making 12
aspirin supp using cocoa butter as the
base, he would weigh
1.77g×12=21.24g of cocoa butter &
0.3g×12=3.6g of ASA
Some Density Factors of
Drugs in Cocoa Butter
Medicaments
Density Factor
Aspirin
1.3
Barbital
1.2
Bismuth salicylate
4.5
Chloral hydrate
1.3
Cocaine hydrochloride
1.3
Codeine phosphate
1.1
Diphenhydramine hydrochloride
1.3
Morphine hydrochloride
1.6
Hand Rolling



The oldest & simplest method of supp
preparation & may be used when only
a few supp are to be prepared in a
cocoa butter base.
It has the advantage of avoiding the
necessity of heating the cocoa butter.
A plastic-like mass is prepared by
triturating grated cocoa butter & API
in a mortar.
Hand Rolling


The mass is formed into a ball in the
palm of the hands, then rolled into a
uniform cylinder with a large spatula
or small flat board on a pill tile.
The cylinder is then cut into the
appropriate number of pieces which
are rolled on one end to produce a
conical shape
Hand Rolling


Effective hand rolling requires
considerable practice & skill.
The supp "pipe" or cylinder tends to
crack or hollow in the center,
especially when the mass is
insufficiently kneaded & softened.
2. Compression Molding


Method of preparing supp from a
mixed mass of grated supp base &
medicaments which is forced into a
special compression mold.
The method requires that the capacity
of the molds first be determined by
compressing a small amount of the
base into the dies & weighing the
finished supp.

When active ingredients are added, it
is necessary to omit a portion of the
supp base, based on the density
factors of the active ingredients
3. Fusion Molding




Involves first melting the supp base, &
then dispersing/dissolving the drug in
the melted base.
The mixture is removed from the heat
& poured into a supp mold.
When the mixture has congealed, the
supp are removed from the mold.
Fusion method can be used with all
supp types & must be used with most
Composition of
Suppository



Generally made from solid ingredients
& drugs which are measured by
weight.
When they are mixed, melted, &
poured into supp mold cavities, they
occupy a V-the volume of the mold
cavity.
Since the components are measured
by weight but compounded by
Density Factor



When a drug is placed in a supp base,
it will displace an amount of base as a
function of its density
If the drug has the same density as
the base, it will displace an equivalent
weight of the base
If the density of the drug is greater
than that of the base, it will displace a
proportionally smaller weight of the
The Density Factor


Density factors for common drugs in
cocoa butter are available in standard
reference texts.
is used to determine how much of a
base will be displaced by a drug.
Aluminum Metal Molds



Come in a variety of cavity sizes &
with a variety of number of cavities
per mold.
Common sizes vary from 1-2.5 g, &
common number of cavities range
from 6 cavities up to 100 cavities.
2 halves of the mold are held together
with either nuts or some molds have 1
centered screw
Plastic Suppository Shells




Come in long strips that can be torn
into any number of cavities.
The supp mixture is poured directly
into the shell up to a mark.
These disposable molds do not need
any lubrication regardless of the
suppository mixture.
When the mixture has hardened, the
plastic mold is heat sealed.
Usage a Suppository



Patient select 1 shell & peel the sides
of the shell off to obtain supp
One advantage of this type of mold: if
the supp should melt, it wont run out
of the mold.
If the material can ongeals again, it
will retain the supp shape. This type of
mold is available in 1-5 g sizes, &
many different colors
Flexible Rubber Molds



When the supp mixture has congealed
in these molds, the finished supp are
"pushed" out of each cavity.
If the prescription does not require all
of the cavities in the strip, it can be
trimmed with scissors.
These flexible rubber molds are ideal if
the supp need to be refrigerated
(shells also are suitable for this