Transcript Suppositories and Inserts

Suppositories and Inserts
Contents
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Suppositories
Some factors of drug absorption from
rectal suppositories
Suppository bases
Preparation of suppositories
Type of suppositories
Packaging and storage
1. Suppositories
Definition: Suppositories are solid dosage
forms intended for insertion into body
orifices where they melt, soften, or dissolve
and exert local or systemic effects.
 Suppositories are commonly used rectally
and vaginally (pessaries) and occasionally
urethral (bougies), rarely nasal (bougies)
and through ear (ear cones).
They have various shapes and weights.
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The shape and size of a suppository must be
such that it can be easily inserted into the
intended orifice without causing undue
distension,
and once inserted, it must be retained for the
appropriate period.
Rectal Suppositories
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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, and enemas.
Using rectal administration to achieve systemic
activity is preferred when the drug is destroyed
in the GI tract, if oral administration is not
possible because of vomiting, or the patient is
unconscious or incapable of swallowing oral
formulations.
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Rectal administration has been used to treat a
variety conditions such as asthma, nausea,
motion sickness, anxiety, and bacterial
infections.
Suppositories are manufactured in a variety of
shapes. Rectal suppositories for adults are
tapered at one end and usually weigh about 2
grams. Infant rectal suppositories usually weight
about 1 gram or about half that of adult
suppositories.
The major disadvantages of rectal suppositories
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1.They are not preferred by patients; they are
inconvenient.
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2.Rectal absorption of most drugs is frequently
erratic and unpredictable.
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3.Some suppositories "leak" or are expelled after
insertion.
Vaginal suppositories
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are employed as contraceptives, feminine
hygiene antiseptics, bacterial antibiotics, or to
restore the vaginal mucosa.
Vaginal suppositories are inserted high in the
vaginal tract with the aid of a special applicator.
The suppositories are usually globular, oviform,
or cone-shaped and weigh between 3 - 5 grams.
Vaginal Suppositories
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Vaginal administration has many advantages.
1.Generally there is less drug degradation via this
route of administration compared to oral
administration
2.The dose can be retrieved if necessary
3.There is the potential of long term drug
absorption with various intrauterine devices
(IUDs).
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Urethral suppositories - called bougies which
are pencil shape.
Those intended for males weigh 4 gm each and are
100-150 mm long.
Those for females are 2 gm each and 60-75 mm in
length.
Nasal suppositories: - called nasal bougies or
buginaria meant for introduction in to nasal cavity.
They are prepared with glycero gelatin base.
They weigh about 1 gm and length 9-10 cm.
Pharmacological Uses:
1） Local action
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Rectal suppositories intended for localized action
are most frequently used to relieve constipation or
the pain, irritation, itching, and inflammation
associated with hemorrhoids or other anorectal
conditions.
A popular laxative, glycerin suppositories promote
laxation by the local irritation of the mucous
membranes.
Vaginal suppositories or inserts intended for
localized effects are employed mainly as
contraceptives, antiseptics in feminine hygiene.
2) Systemic action
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For systemic effects, the mucous membranes of
the rectum and vagina permit the absorption of
many soluble drugs.
Although the rectum is used frequently as the site
for the systemic absorption of drugs, the vagina is
not as frequently used for this purpose.
Examples include paracetamol
(acetoaminophen), diclofenac.
Normal shapes and weight of rectal suppositories: For adults weigh 2 gm and are torpedo shape.
 Children's suppositories weigh about 1 gm.
Among the advantages (Merits) over oral therapy
of the rectal route of administration for achieving
systemic effects are these:
a) Drugs destroyed or inactivated by the pH or
enzymatic activity of the stomach or intestines
need not be exposed to this destructive
environments;
b) Drugs irritating to the stomach (or insatiable)
may be giving without causing such irritation
c) Drugs destroyed by portal circulation may bypass
the liver after rectal absorption
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d) The route is convenient for administration of
drugs to adult or pediatric patients who may be
unable or unwilling to swallow medication or
unconscious patient)
e) It is an effective route in the treatment of patients
with vomiting episodes.
f) Prolong drug release.
Disadvantages (Limitations)of suppositories:
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Aesthetic objection
Leakage
Unpredictable absorption
Mucosal damage
2. Some factors of drug absorption from
rectal suppositories
1) Physiologic factors
 Colonic content
- when deemed desirable, an evacuant enema
may be administered and allowed to act
before the administration of a suppository of
a drug to be absorbed.
- Diarrhea, colonic obstruction, and tissue
dehydration
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Circulation route
The lower hemorrhoidal veins surrounding
the colon receive the absorbed drug and
initiate its circulation throughout the body,
bypass the liver.
Lymphatic circulation also assists in the
absorption of rectally administered drugs.
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pH and lack of buffering
Because rectal fluids are essentially neutral
in pH and have no effective buffer capacity,
the form in which the drug is administered
will not generally be chemically changed by
the rectal environment.
The suppository base employed has a
marked influence on the release of active
constituents incorporated into it.
Composition of suppositories
• Drug (active ingredient)
• Base
• Other additives – surfactants,
soothing agents, antioxidants,
preservatives, anti-settling agents
(blend of higher m.p waxes & fatty
acids )
2) Physicochemical factors of the drug and
suppository base
 Lipid-water solubility
- A lipophilic drug that is distributed in a fatty
suppository base in low concentration has
less of a tendency to escape to the
surrounding aqueous fluids than would a
hydrophilic substance present in a fatty base
to an extent approaching its saturation.
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Water soluble bases, for example, PEG,
which dissolve in the anorectal fluids,
release for absorption both water-soluble
and oil-soluble drugs.
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Naturally, the more drug a base contains,
the more drug will be available for potential
absorption.
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Particle size
For drugs present in a suppository, the size
of the drug particle will influence its rate of
dissolution and its availability for absorption.
The smaller the particle size, the more
readily the dissolution of the particle and the
greater the chance for rapid absorption.
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Nature of the base
The possiblity of chemical and/or physical
interactions between the medicinal agent
and the suppository base, which could affect
the stability and/or bioavailability of the
drug.
If the base is irritating to the mucous
membranes of the rectum, it may initiate a
colonic response and prompt a bowel
movement, negating the prospect of
complete drug release and absorption.
3. The ideal suppository bases
One of the first requisites for a suppository
base is that (ideal suppository base)
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it remains solid at room temperature
Release medicament readily soon after insertion.
Easily melt and dissolve or disperse at body temp.
Retain shape while handling moldable, non adhering
Non-toxic & non-irritant
Stable & compatible
Classification of suppository bases
I. Oleaginous (fatty-lipophilic) bases
a) Natural - cocoa butter or their substitute
b) Synthetic - witepsol, massuppol
II. Hydrophilic (water soluble/miscible) bases
a) Natural - glycero gelatin (Glycerinated gelatin
b) Synthetic –PEG- macrogols
1) Fatty or oleaginous base
Cocoa butter or Theobroma Oil
 is defined as the fat obtained from the roasted
seed of Theobroma cacao.
 At room temperature it is a yellowish, white
solid having a faint, agreeable chocolate-like
odor.
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Chemically, it is a triglyceride
At ordinary room temperatures of 15 to 25C,
it is a hard, amorphous solid
Cocoa butter melts between 30C to 36C, it
is an ideal suppository base.
Readily liquefiable on warming and rapid
setting on cooling
Cocoa butter exhibits marked polymorphism.
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Two factors when preparing suppositories with
cocoa butter base. First, this base must not be heated
above 35C because cocoa butter is a polymorphic
compound and if overheated will convert to a metastable
structure that melts in the 25 to 30C range. Thus, the
finished suppositories would melt at room temperature
and not be usable.
The second factor is the change in melting point caused
by adding certain drugs to cocoa butter suppositories. For
example, chloral hydrate and phenol tend to lower the
melting point. It may be necessary to add spermaceti or
beeswax to raise the melting point of finished
suppositories back to the desired range.
Limitations:
- Polymorphism – unstable gamma/beta forms
- Adhere to mould due to contractility on solidification
- Softening point too low for hot climates (beeswax may be added)
- Batch to batch variation in composition
- Becomes rancid on storage
- Immiscible in body fluids and poor water absorption
- Tendency to leak, immiscibility makes it not suitable for vaginal
and urethral route
- May melt at warmer climates
Synthetic lipophilic bases advantages & disadvantages:
- readily available
- do not become rancid
- chemically more inert
- do not exhibit polymorphism
- good water absorption and emulsification properties
- lubrication can be avoided
- white, smooth & odorless
- may become brittle & fracture if cooled rapidly
- more expensive than cocoa butter
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Hydrogenated fatty acids of vegetable oils
(palm oil and cottonseed oil)
Fat-based compounds containing higher
molecular weight fatty acids, such as
palmitic and stearic acids with glycerin the
(glyceryl monostearate and glyceryl
monopalmitate, (Witepsol®) )