Dosage Chapter 12 - Suppositories, Inserts and Sticks

Suppositories

a solid dosage form in which one or more
APIs are dispersed in a suitable base and
molded or otherwise formed into a suitable
shape for insertion into the rectum to provide
local or systemic effect.

Suppositories

Intended for insertion into body orifices where they melt, soften, or dissolve and exert local or systemic effects.

Latin ‘supponere’

→ “to place under,” as derived
from sub (under) and ponere (to place

Suppositories

They are meant both linguistically and
therapeutically to be placed under the body, as
into the rectum.

insert

a solid dosage form that is inserted into a
naturally occurring (nonsurgical) body cavity
other than the mouth or rectum, including the
vagina and urethra.

sticks

They are a convenient form for administering
topical drugs. Their development is interesting because it involves the history of cosmetics, which parallels human history.

- easily inserted into the intended orifice
without causing undue distension
- once inserted, it must be retained for the
appropriate period

Why do suppositories, inserts and sticks come in various shapes and weights?

- about 32 mm (1.5 inch) long
- Cylindrical
- have one or both ends tapered
- also shaped like a bullet, a torpedo, or the little
finger

rectal sup size

- (Adult) about 2 g when cocoa butter
(theobroma oil) is employed as the base
- (infants and children) about half the weight and
size of the adult suppositories (pencil shaped)

rectal sup weight

- globular, oviform, or cone shaped
- weigh about 5 g when cocoa butter is the base

Vaginal Inserts size and weight

Vaginal Inserts

formerly called suppositories or
pessaries

- slender, pencil-shaped suppositories
- Male urethral suppositories may be 3 to 6 mm
in diameter and approximately 140 mm long
- When cocoa butter is employed as the base, the
se suppositories weigh about 4 g

urethral bougies size and weight (male)

- slender, pencil-shaped suppositories
- Female urethral suppositories are about half the
length and weight of the male urethral sup,
being about 70 mm long
- Weigh about 2 g when made of cocoa butter

urethral bougies size and weight (female)

-cylindrical in shape and generally range from 5
to 25 g
- packaged in an applicator tube for topical
administration
- applicator can be adjusted to continually
expose new, fresh stick from inside the tube.

medication sticks size and weight

1. First-pass effect: Avoiding, at least partially, the
first-pass effect that may result in higher blood
levels for those drugs subject to extensive first-
pass metabolism upon oral administration.
2. Drug stability: Avoiding the breakdown of certain
drugs that are susceptible to gastric degradation.
3. Large dose drugs: Ability to administer somewhat
larger doses of drugs than using oral admin.
4. Irritating drugs: Ability to administer drugs that
may have an irritating effect on the oral or gas
trointestinal mucosa when administered orally.
5. Unpleasant tasting or smelling drugs: Ability to
administer unpleasant tasting or smelling
drugs whose oral administration is limited.
6. In children, the rectal route is especially useful.
An ill child may refuse oral medication and
may fear injections.
7. In patients experiencing nausea & vomiting or
when the patient is unconscious.
8. The presence of disease of the upper GI tract
that may interfere with drug absorption.
9. Objectionable taste or odor of a drug (esp
important in children).
10.Achievement of a rapid drug effect systemically
(as an alternate to injection).

advantages of rectal administration

1. A perceived lack of flexibility regarding dosage of commercially available suppositories resulting in underuse and a lack of availability.
2. If suppositories are made on demand, they may be expensive.
3. Suppositories as a dosage form are safe, but they
exhibit variable effectiveness, depending upon many factors, including pathology of the anorectal lesions.
4. Different formulations of a drug with a narrow safety margin, such as aminophylline, cannot be interchanged without risk of toxicity
5. The “bullet-shaped” suppository after insertion
can leave the anorectal site and ascend to the
rectosigmoid and descending colon.
6. Defecation may interrupt the absorption
process of the drug; this may especially occur
if the drug is irritating.
7. The absorbing surface area of the rectum is
much smaller than that of the small intestine.
8. The fluid content of the rectum is much less
than that of the small intestine, which may affe
ct dissolution rate, etc.
9. There is the possibility of degradation of some
drugs by the microflora present in the rectum.
10.The dose of a drug required for rectal admin
may be greater than or less than the dose of
the same drug given orally.
11. The factors that affect the rectal absorption of
a drug administered in the form of a
suppository may be divided into two main
groups:
(a) anatomic and physiologic factors
(b) physicochemical factors of the drug and the
base.

disadvantages of suppositories

local action (uses and application)

- Once inserted, the suppository base melts,
softens, or dissolves, distributing its
medicaments to the tissues of the region.
- These medicaments may be intended for
retention within the cavity for local effects, or
they may be intended to be absorbed for
systemic effects.

- Relieve constipation
- Relieve pain
- Relieve irritation
- Relieve itching
- Relieve inflammation

Rectal suppositories intended for local action

systemic action (uses and application)

- Mucous membranes of the rectum and vagina
permit the absorption of many soluble drugs.
- The rectum is used frequently as the site for the
systemic absorption of drugs
- But the vagina is not as frequently used for this
purpose.

Mucous membranes

___________ of the rectum and vagina
permit the absorption of many soluble drugs.

rectum

The ______ is used frequently as the site for the
systemic absorption of drugs

• sodium salicylate

• chloral hydrate

• methylene blue

• atropine, morphine

absorbed better rectally than orally

• iodides

• tetracycline hydrochloride

• sodium penicillin G

absorbed better orally than rectally

• sulfanilamide in a glycerinated gelatin base

• prednisone

oral and rectal absorptions comparable

- Circulation route
- Colonic contents
- pH and lack of buffering capacity of the rectal
fluids

physiological factors and drug effect

1. Lipid–Water Solubility
2. Particle size

physicochemical factors and drug effect

it should remain solid at RT but soften, melt, or dissolve readily at body temperature so that the drug is fully available soon after insertion.

Important characteristic of base

cocoa butter (theobroma oil)

melts quickly at body temperature, but because it is immiscible with body fluids, fat-soluble drugs tend to remain in the oil and have little tendency to enter the aqueous physiologic fluids.

For water-soluble drugs in cocoa butter

usually true and good release results (suppository bases)

Fat-soluble drugs

released more readily from bases of glycerinated gelatin or polyethylene glycol, both of which dissolve slowly in body fluids.

cocoa butter

When irritation or inflammation is to be relieved, as in the treatment of anorectal disorders, ______ appears to be the superior base because of its emollient or soothing, spreading action.

- physically and chemically stable
- Nonirritating, Nontoxic
- Nonsensitizing, Chemically and physiologically inert
- Compatible with a variety of drugs, stable during storage,
and esthetically acceptable (free from objectionable odor
and a pleasing appearance)

A suppository base should be:

1. Fatty or Oleaginous Bases
2. Water-Soluble and Water-Miscible Bases
3. Miscellaneous bases

classification of bases

34-35 degree celsius

melting range of cocoa butter

35.5-37 degree celsius

melting range of fattibase

60-71 degree celsius

melting range of polybase

33-35 degree celsius

melting range of suppocire OSI

31.7-32.8 degree celsius

melting range of wecobee W

33-35 degree celsius

melting range of witepsol H15

cocoa butter

base that is composed of mixed triglycerides of oleic, palmitic, stearic acids

fattibase

base that is composed of triglycerides from palm, palm kernel, and coconut oils with self-emulsifying glyceryl monostearate and polyoxyl stearate

polybase

base that is composed of a homogeneous blend of PEGs and polysorbate 80

suppocire OSI

base that is composed of eutectic mixtures of mono-, di- triglycerides derived from natural vegetable oils, each type having slightly different properties

wecobee W

base that is composed of triglycerides derived from coconut oil

witepsol H15

base that is composed of triglycerides of saturated fatty acids C12-C18 with varied portions of the corresponding partial glycerides

(a)Molding from a melt
(b)Hand rolling and shaping

preparation of suppositories

(a) melting the base
(b) incorporating any required medicaments
(c) pouring the melt into molds
(d) allowing the melt to cool and congeal into
suppositories
(e) removing the formed suppositories from the
mold.

molding steps

calibration

The first step in _______ of a mold is to prepare molded suppositories from base material alone. After removal from the mold, the suppositories are weighed, and the total weight and average weight of each suppository are recorded (for the particular base used)

lubrication

Depending on the formulation, suppository molds may require ______ before the melt is poured to facilitate clean and easy removal of the molded suppositories.

Lubrication

_________is seldom necessary when the base is cocoa butter or polyethylene glycol, as these materials contract sufficiently on cooling to separate from the inner surfaces and allow easy removal.

glycerinated gelatin.

Lubrication is usually necessary with ________

volume of base required.

Because the volume of the mold is known (from the
determined volume of the melted suppositories formed from the base), the volume of the drug
substances subtracted from the total volume of the
mold will give the _________.

Hand rolling and shaping

is a historic part of the art of the pharmacist

suppositories with vegetable extracts

Major Changes in Suppository Characteristics
Due to Natural Aging and the Causes

Modification: odor

Causes: fungal contamination

Examples: ________

suppositories with tartrazine yellow aqueous solution

Major Changes in Suppository Characteristics
Due to Natural Aging and the Causes

Modification: color

Causes: discoloration due to oxidation

Examples: ________

suppositories with essential oils

Major Changes in Suppository Characteristics
Due to Natural Aging and the Causes

Modification: shape

Causes: incorrect temperature during storage

Examples: ________

suppositories with vegetable extracts or caffeine based suppositories

Major Changes in Suppository Characteristics
Due to Natural Aging and the Causes

Modification: surface condition

Causes: whitening

Examples: ________

suppositories with camphor, menthol, etc.

Major Changes in Suppository Characteristics
Due to Natural Aging and the Causes

Modification: weight

Causes: loss of volatile substances

Examples: ________