DOSAGE: CHAPTER 12 (Suppositories, Inserts, and Sticks)

SUPPOSITORIES

- It is 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.

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

SUPPOSITORIES

Latin'supponere' "to place under," as derived from sub (under) and ponere (to place)

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

INSERT

- It is 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.

glycerin suppositories

laxative for babies

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.

SUPPOSITORY, INSERT AND STICK SHAPES
Why do they come in various shapes and
weights?

- easily inserted into the intended orifice
without causing undue distension

- once inserted, it must be retained for the
appropriate period

Rectal sup-

through fingers

Vaginal

fingers or an applicator

SUPPOSITORY, INSERT AND STICK SHAPES
SIZE
Rectal sup

- 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

SUPPOSITORY, INSERT AND STICK SHAPES
WEIGHT

Rectal sup

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)

SUPPOSITORY, INSERT AND STICK SHAPES
SIZE & WEIGHT

Vaginal Inserts (formerly called suppositories or pessaries)

- globular, oviform, or cone shaped

- weigh about 5 g when cocoa butter is the base

SUPPOSITORY, INSERT AND STICK SHAPES
SIZE & WEIGHT
Urethral Inserts (bougies)

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, these suppositories weigh about 4 g

SUPPOSITORY, INSERT AND STICK SHAPES
SIZE & WEIGHT

Urethral Inserts (bougies)

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

SUPPOSITORY, INSERT AND STICK SHAPES
SIZE & WEIGHT
Medication sticks

- 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.

ADVANTAGES OF RECTAL ADMINISTRATION
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.

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).

DISADVANTAGES OF SUPPOSITORIES
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.

USES AND APPLICATION
LOCAL ACTION

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.

USES AND APPLICATION
LOCAL ACTION
- Rectal suppositories intended for local action

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

USES AND APPLICATION
SYSTEMIC ACTION

- 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.

SOME FACTORS OF DRUG ABSORPTION
FROM RECTAL SUPPOSITORIES

PHYSIOLOGICAL FACTORS AND DRUG EFFECT

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

SOME FACTORS OF DRUG ABSORPTION
FROM RECTAL SUPPOSITORIES
PHYSICOCHEMICAL FACTORS AND DRUG EFFECT

1. Lipid-Water Solubility
2. Particle size

SUPPOSITORY BASES

Important characteristic of base: 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.

- cocoa butter (theobroma oil) melts quickly at body temperature, but because it is immiscible with body fluids, fat-solu
ble drugs tend to remain in the oil and have little tendency to enter the aqueous physiologic fluids.

SUPPOSITORY BASES
For water-soluble drugs in cocoa butter

usually true and good release results

Fat-soluble drugs

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

When irritation or inflammation is to be relieved

as in the treatment of anorectal disorders, cocoa butter appears to be the superior base because of its emollient or soothing, spreading action

NATURE OF BASES
A suppository base should be:

- 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)

CLASSIFICATION OF BASES

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

FORMULATION VARIABLES

a) the nature and form of the active principle
(esters, salts, complexes, etc.)

b) the physical state, particle dimensions, the
specific surface of the product

c) solubility of the drug in various bases

d) presence or absence of adjuvants added to the active principle

e) nature and type of dosage form in
which the active principle is incorporated

f) pharmaceutical procedures used in the
preparation of the dosage form.

PREPARATION OF SUPPOSITORIES

(a) Molding from a melt

(b)Hand rolling and shaping

PREPARATION OF SUPPOSITORIES
MOLDING STEPS

(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.

PREPARATION OF SUPPOSITORIES

Partially opened mold capable of producing 50 torpedo-shaped suppositories in a single molding (Courtesy of Gallipot, Inc.).

CALIBRATION OF THE MOLD

• The pharmacist should calibrate each suppository mold for the usual base (generally cocoa butter and a polyethy
lene glycol base) so as to prepare medicated supp each having the proper quantity of medicaments.

• The first step in calibration 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 OF THE MOLD

• Depending on the formulation, suppository molds may require lubrication 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.

• Lubrication is usually necessary with glycerinated gelatin.

Determination of the Amount of Base
Required

• In determining the amount of base to be
incorporated with the medicaments, the pharmacist must be certain that the required amount of drug is provided in each suppository.

• 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 volume of base required.

HAND ROLLING AND SHAPING

With ready availability of suppository molds
of accommodating shapes and sizes, there is
little requirement for today's pharmacist to
shape suppositories by hand.

• Hand rolling and shaping is a historic part of
the art of the pharmacist.