Compounding Rectal Dosage Forms,

d.
INTRODUCTION
Rectal administration is not often the first route of choice; but it
becomes a good alternative when the oral route is inadvisable. Relatively
low cost and lack of technical difficulties make rectal drug
administration attractive when compared to parenteral therapy.
The downside of rectal administration includes the esthetics and
stigma of violating the patient’s dignity. This, along with potential
rectal irritation due to frequent administration, and difficulty in
titrating a correct dose due to limited strengths of commercial rectal
dosage forms pose some challenges.
Psychologically, rectal dosage forms can provide a considerable
placebo effect in the treatment of anorectal disorders. The user
feels that something is really being done at the involved site and
this can produce a positive attitude towards this mode of treatment
of the disease or disorder. This may promote hope and the
possibility of avoiding the embarrassment of telling the family and
friends of what is happening in the private area.
Previously, the rectal pathway was reserved for the administration
of locally active products such as those in the treatment of hemor-
Quest Educational Services Inc. is accredited by the
Accreditation Council for Pharmacy Education as a
provider of continuing pharmaceutical education.
ACPE No. 748-000-06-003-H01
This lesson is no longer valid for CE credit after 12/01/09.
GOALS AND OBJECTIVES
Goal: To provide information and support for dosage forms that can be compounded and administered rectally.
Objectives: After reading and studying the article, the reader will be able to:
1.List at least five advantages to the rectal administration of drugs.
2.Describe the anatomy and physiology of the rectum.
3.Discuss the factors involved in drug release from different matrices administered rectally.
4.Discuss the characteristics of enemas, microenemas, gels, ointments and aerosols administered rectally.
5.Describe the formulation variables that must be considered in compounding rectal dosage forms.
Compounding Rectal Dosage Forms, Part I
Loyd V. Allen, Jr., Ph.D., R.Ph.
! Professor Emeritus, University of Oklahoma College of Pharmacy
! Editor in Chief, International Journal of Pharmaceutical Compounding
! Dr. Allen is not affiliated with Paddock Laboratories Inc.
rhoids, worms and constipation. In the treatment of hemorrhoids
and anal fissures, a suggestion was made at one time that a suppository
should be “hour glass” or “collar button” shaped so that
the suppository would stay in the anal canal.
Now, it is well accepted that many active ingredients can be administered
rectally and achieve therapeutic blood levels from any of
several different dosage forms. Some medications are best administered
by this route while others can be if needed.
Advantages to Rectal Administration:
The advantages to rectal administration include the following.
1. First pass effect - Avoiding, at least partially, the first pass
effect which 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 administration.
4. Irritating drugs - Ability to administer drugs which may
have an irritating effect on the oral or GI 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. Rectal administration can be especially useful in terminal
care.
fore the pH of the medium may be determined by the characteristics
of the drug and the dosage form.
FORMULATION VARIABLES
Active drugs have a number of physical characteristics that can
affect efficacy. For rectal dosage forms, those of interest involve the
following:
1. The nature and form of the active principle (esters, salts,
complexes, etc).
2. The physical state, particle dimensions and the specific
surface of the product.
3. The presence or absence of adjuvants added to the active
principle.
4. The nature and type of dosage form in which the active
principle is incorporated.
5. Pharmaceutical procedures used in the preparation of the
dosage form.
Physical State: An active drug can be either a solid, liquid or semisolid
in nature. For solids, the drug’s particle size may be very
important, especially if the drug is not very water soluble; the
increase in surface area resulting from decreased particle size can
serve to enhance its activity.
Solubility: Whether or not the active ingredient is soluble in the
vehicle can alter the manufacturing and compounding processes in
several ways. Increased solubility of the active in the base can
improve product homogeneity; however, it may also delay the
release of the active if there is too great an affinity of the drug for
the vehicle. In some cases, it may be desired to retain the drug in the
rectal cavity for a longer time and this can be accomplished if the
drug has a greater affinity for the vehicle than for migrating to the
mucosal surface for absorption or to produce a local effect.
If the active ingredient is insoluble in the vehicle, as is the case
when a “suspension” or “emulsion” is formed, this poses different
problems. It is necessary to maintain homogeneity of the total mixture;
this can usually be obtained by constant agitation of the
mixture during processing and filling. Emulsions can be handled
through the proper use of surfactants to obtain a homogenous mixture.
Related to the water solubility of a drug can be the rate of diffusion
across the rectal membrane. A drug with high water solubility
quickly leaves the vehicle, producing a high concentration in the
intrarectal phase which supports a high diffusion rate across the
barrier. A drug with low water solubility saturates the intrarectal
phase at a low concentration resulting in low diffusion and subsequent
low dissolution of the drug particles remaining in the melted
excipient. Drugs with low solubility in water may result in low
availability, while drugs with good solubility may give a rapid and
intense therapeutic response with the dose administered.1
A number of factors affect the decisions the pharmacist must make
when preparing a rectal dosage form. Questions the pharmacist
should ask before formulating this dosage form include the following:
! Is the desired effect to result from systemic or local use?
! Is the dosage form a liquid, semisolid or solid?
! Is a rapid or a slow and prolonged release of the
medication desired?
Drugs for local effect may include the treatment of hemorrhoids,
local anesthetics, antiseptics, antibiotics, and antifungals. Drugs for
systemic effect include analgesics, antiasthmatics, antinauseants,
antiepileptics, hormones and others.
The selection of a vehicle is dependent upon a number of physicochemical
variables, including the characteristics of the drug, the
base and other excipients that are present.
Rectal administration provides for a rapid, and in many cases,
extensive absorption of the active ingredient. The rapidity, intensity
and duration of action are three parameters which must be considered
during formulation for rectal administration and, in many
cases, can be altered to meet the needs of the individual patient.
Anatomical and Physiological Considerations
The rectum consists of the last few inches of the large intestine, terminating
at the anus. The wall of the GI tract consists of several
layers, including the mucosa, submucosa, tunica muscularis and the
visceral peritoneum. The mucous membrane of the rectum, where
rectal dosage forms are generally administered, is made up of a
layer of cylindrical epithelial cells, differentiated from those of the
intestine by the absence of villi.
The rectum contains three types of hemorrhoidal veins, namely the
superior hemorrhoidal vein, middle hemorrhoidal vein, and the
inferior hemorrhoidal vein. These veins act by transporting the
active principle absorbed in the rectum to the blood system either
directly by means of iliac veins and the vena cava (inferior and middle
hemorrhoidal veins) or indirectly by means of the portal vein
and the liver (superior hemorrhoidal vein).
The three hemorrhoidal veins are linked by an anastomosis network.
Since it is not really possible to predict the position or exact
location of the dosage form in the rectum, it is not really possible to
predict exactly which way the active principle will be transported. It
may preferably be by one pathway or another or a combination.
However, it is generally accepted that at least 50% to 70% of the
active ingredients administered rectally take the direct pathway,
thus bypassing the liver and avoiding the first-pass effect. There is
also the possibility of absorption into the lymphatic vessels that
should not be dismissed, but may be minimal.
Physiology
The physiological factors likely to affect rectal absorption are the rectal
liquid pH and the rectal liquid buffering capacity. The rectal
mucosal fluid has a pH very close to neutral and has a low buffer
capacity. Hence, after administration of the suppository, the pH of
the rectal liquid may be determined by the active principle being
used. These facts lead us to conclude that the addition of buffering
agents of a suitable pH range to the suppositories could, in some
cases, increase active principle absorption.
When empty of fecal material, the rectum contains only 2 to 3 mL of
inert mucosal fluid. In the resting state, the rectum is nonmotile and
there are no villi or microvilli present on the rectal mucosa. However,
there is abundant vascularization of the submucosal region of the
rectum wall with blood and lymphatic vessels.
Among the physiologic factors that affect drug absorption from the
rectum are the colonic contents, circulation route, and the pH and
lack of buffering capacity of the rectal fluids.
Colonic Content: When systemic effects are desired from the
administration of a medication, greater absorption may be expected
from a rectum that is void than from one that is distended with fecal
matter. A drug will obviously have greater opportunity to make
contact with the absorbing surface of the rectum and colon in the
absence of fecal matter. Therefore, when deemed desirable, an evacuant
enema may be administered and allowed to act before
administration of a suppository of a drug to be absorbed. Other conditions
such as diarrhea, colonic obstruction due to tumorous
growths, and tissue dehydration can all influence the rate and
degree of drug absorption from the rectal site.
Circulation route: It is estimated that about 50-70% of the dose of a
rectal dosage form that is absorbed will bypass the liver into the
general circulation.
pH and Lack of Buffering Capacity of the Rectal Fluids: Because
rectal fluids are essentially neutral in pH (7–8) and have negligible
buffer capacity, the form in which the drug is administered will not
generally be chemically changed by the rectal environment; there-
Drug Release: The rate of drug release is an important factor in the
selection of a vehicle. If a drug does not release its medication
within 6 hours, the patient may not receive its full benefit, as the
drug remaining in the rectum may be expelled. Thus, among the
factors that must be considered in the selection of a suppository
base is the drug’s solubility. One way to ensure maximum release
of the drug from the base is to apply the principle of opposite characteristics,
i.e., water soluble drugs should be placed in oil soluble
bases while oil soluble drugs should be placed in water soluble
bases.
Drug release rate requirements are especially important in the
selection of the suppository base. Other factors must also be considered
when preparing a suppository. They include the presence
of water, hygroscopicity, viscosity, brittleness, density, volume
contraction, special problems, incompatibilities, pharmacokinetics,
and bioequivalence.
Presence of Water: When preparing nonaqueous rectal dosage
forms, the pharmacist should avoid using water to incorporate an
active drug as water may accelerate the oxidation of fat, increase
the degradation rate of many drugs, enhance reactions between
the drug and other components, support bacterial/fungal growth,
and require the addition of bacteriostatic agents. Furthermore, if
the water evaporates, the dissolved substances may crystallize and
possibly become irritating upon insertion.
Hygroscopicity: Glycerin and polyethylene glycol containing
vehicles are hygroscopic. The rate of moisture change is dependent
on the chain length of the molecule as well as the temperature and
humidity of the environment.
Viscosity: Viscosity considerations are also important in the
preparation and the release of the drug. If the viscosity of a base is
low, it may be necessary to add a thickening agent to ensure uniformity
of the drug in the vehicle. After the dosage form has been
administered, the release rate of the drug may be slowed if the viscosity
of the vehicle is very high. This is because the viscosity
causes the drug to diffuse more slowly through the base to reach
the mucosal membrane for absorption.
Brittleness: Brittle suppositories can be difficult to handle, wrap,
and use. In general, brittleness results when the percentage of nonbase
materials exceeds about 30%. Synthetic fat bases with high
stearate concentrations or those that are highly hydrogenated are
typically more brittle. Shock cooling also causes fat and cocoa butter
suppositories to crack. This condition can be prevented by
ensuring that the temperature of the mold is as close to the temperature
of the melted base as possible. Suppositories should not
be placed in a freezer, which also causes shock cooling. The addition
of a small quantity (usually less than 2%) of Tween 80, Tween
85, fatty acid monoglycerides, castor oil, glycerin, or propylene
glycol will make these bases more pliable and less brittle.
ENEMAS/MICROENEMAS
(SOLUTIONS/SUSPENSIONS)
Enemas
Enemas are dosage forms designed to be administered rectally for
clearing out the bowel or for administration of drugs or food. An
enema is a method of administration and may involve solutions,
suspensions, emulsions, foams, and gels. Generally, there are two
types: retention enemas and evacuation enemas.
Retention Enemas: A number of solutions, suspensions and emulsions
are administered rectally for the local effects of the medication
(e.g., hydrocortisone) or for systemic absorption (e.g., aminophylline).
In the case of aminophylline, the rectal route of
administration minimizes the undesirable gastrointestinal reactions
associated with oral therapy. Clinically effective blood levels of the
agents are usually obtained within 30 minutes following rectal
instillation. Corticosteroids can be administered as retention enemas
as adjunctive treatment of some patients with ulcerative colitis.
Evacuation Enemas: Rectal enemas are used to cleanse the bowel.
Commercially, many enemas are available in disposable plastic
squeeze bottles containing a premeasured amount of enema solution.
The agents present are solutions of sodium phosphate and sodium
biphosphate, glycerin and docusate potassium, and light mineral oil.
Enemas may be prepared as solutions, suspensions, emulsions etc.
Solutions: Considerations in preparing solutions include solubility,
solvent selection, pH, osmolality and stability of the drug. If the pH is
too low or too high, it may be irritating to the mucosa. If the solution is
hyperosmolar, it may pull fluids from the local area and initiate a defecation
reflex.
Suspensions: Suspensions are preparations containing finely divided
drug particles distributed somewhat uniformly throughout a vehicle in
which the drug exhibits a minimum degree of solubility. In most good
pharmaceutical suspensions, the particle diameter is between 1 and 50
microns. The pharmacist may have to use a solid dosage form, e.g.,
tablet, capsule, of the drug and extemporaneously compound a liquid
preparation, or it can be made from the bulk powder.
Typically, when formulating an extemporaneous suspension, the contents
of a capsule, crushed tablets, or bulk powder is placed in a
mortar. The selected vehicle is then slowly added to and mixed with
the powder to create a paste and then diluted to the desired volume.
To minimize stability problems of the extemporaneously prepared
product, it should be placed in air-tight, light-resistant containers by
the pharmacist and subsequently stored in the refrigerator by the
patient. Because it is a suspension, the patient should be instructed to
shake it well prior to use and on a daily basis watch for any color
change or consistency change that might indicate a stability problem
with the formulation.
The following examples of rectal suspensions have frequently been
compounded by pharmacists when not commercially available. Barium
Sulfate for Suspension, USP has been employed orally or rectally
for the diagnostic visualization of the gastrointestinal tract.
Mesalamine (i.e., 5-aminosalicylic acid) suspension was introduced
onto the market in 1988 as Rowasa® (Solvay) for treatment of Crohn’s
disease, distal ulcerative colitis, proctosigmoiditis, and proctitis.
Emulsions: An emulsion is a dispersion in which the dispersed phase
is composed of small globules of a liquid distributed throughout a
vehicle in which it is immiscible. Pharmaceutically, the process of
emulsification enables the pharmacist to prepare relatively stable and
homogeneous mixtures of two immiscible liquids. It permits the
administration of a liquid drug in the form of minute globules rather
than in bulk.
The initial step in preparation of an emulsion is the selection of the
emulsifier. Among the emulsifiers and stabilizers for pharmaceutical
systems are some carbohydrate materials (acacia, tragacanth, agar,
chondrus, and pectin), protein substances (gelatin, egg yolk, and
casein), high molecular weight alcohols (stearyl alcohol, cetyl alcohol,
and glyceryl monostearate), wetting agents (which may be anionic,
cationic, or nonionic), and finely divided solids (colloidal clays including
bentonite, magnesium hydroxide, and aluminum hydroxide).
Emulsions may be prepared by several methods, depending upon the
nature of the emulsion components and the equipment available for
use. On a small scale, as in the laboratory or pharmacy, emulsions may
be prepared using a dry Wedgewood or porcelain mortar and pestle, a
mechanical blender or mixer such as a Waring blender or a milk-shake
mixer, a hand homogenizer, a bench-type homogenizer, or sometimes
a simple prescription bottle. On a large scale, large volume mixing
tanks may be used to form the emulsion through the action of a highspeed
impeller. As desired, the product may be rendered finer by
passage through a colloid mill, in which the particles are sheared
between the small gap separating a high speed rotor and the stator, or
by passage through a large homogenizer, in which the liquid is forced
under great pressure through a small valve opening.
Microenemas
A microenema, also called rectal tube, is a more concentrated
form of a drug generally administered for a systemic effect. As
an example, diazepam microenemas (Stesolid® in Europe) are
available, generally containing about 5 mg/mL diazepam in
solution. Diazepam microenemas are generally used in the management
of selected, refractory patients with epilepsy, on stable
regimens of antiepileptic drugs, who require intermittent use of
diazepam to control occasional breakthrough seizures.
Microenemas can be easily prepared by adding thickening
agents to injectable solutions. This provides the dose of a drug
in a reasonably small volume of generally 1 to 5 mL. Microenemas
can be administered by attaching a short length of tubing to
a syringe in which the microenema has been placed. The tubing
is lubricated and inserted rectally, followed by depressing the
plunger to deliver the drug. As an alternative, the microenema
can be placed in a plastic bulb-device where the tip is lubricated
and then inserted rectally and the bulb squeezed to expel the
drug.
GELS
Gels are semisolid systems consisting of dispersions made up of
either small inorganic particles or large organic molecules
enclosing and interpenetrated by a liquid. Some gel systems are
as clear as water in appearance and others are turbid, since the
ingredients involved may not be completely molecularly dispersed
(soluble or insoluble) or they may form aggregates,
which disperse light. The concentration of the gelling agents is
mostly less than 10%, usually in 0.5 to 2.0% range, with some
exceptions.
Gels may be prepared by the direct hydration in water of the
inorganic chemical, the hydrated form constituting the disperse
phase of the dispersion. Examples of gelling agents include acacia,
alginic acid, bentonite, carbomer, carboxymethylcellulose
sodium, cetostearyl alcohol, colloidal silicon dioxide, ethylcellulose,
gelatin, guar gum, hydroxyethylcellulose, hydroxypropyl
cellulose, hydroxypropyl methylcellulose, magnesium aluminum
silicate, maltodextrin, methylcellulose, polyvinyl
alcohol, povidone, propylene carbonate, propylene glycol alginate,
sodium alginate, sodium starch glycolate, starch,
tragacanth and xanthan gum.
In gel preparation, the powdered polymers, when added to
water, may form temporary gels that slow the process of dissolution.
As water diffuses into these loose clumps of powder,
their exteriors frequently turn into clumps of solvated particles
encasing dry powder. The globs or clumps of gel dissolve very
slowly because of their high viscosity and low diffusion coefficient
of the macromolecules.
Rectal lubricating jellies are used to assist in medical procedures,
to aid in insertion of various devices and drugs, including
catheters and suppositories, and as vehicles for some drug products,
especially in extemporaneous compounding.
RECTAL OINTMENTS
The use of rectal ointments is generally limited to the treatment
of local conditions. Ointments can be for topical application to
the perianal area and for insertion within the anal canal. They
mostly are used to treat local conditions of anorectal pruritus,
inflammation and the pain and discomfort associated with hemorrhoids.
The drugs employed include astringents (e.g., zinc
oxide), protectants and lubricants (e.g., cocoa butter, lanolin),
local anesthetics (e.g., pramoxine HCl), and antipruritics and
anti-inflammatory agents (e.g., hydrocortisone).
The bases used in anorectal ointments and creams include combinations
of polyethylene glycol 300 and 3350, emulsion cream
bases utilizing cetyl alcohol and cetyl esters wax, and white
petrolatum and mineral oil. When antimicrobial preservatives
are required, methylparaben, propylparaben, benzyl alcohol,
and butylated hydroxyanisole (BHA) are frequently used.
Before applying rectal ointments and creams to the perianal
skin, the affected area should be cleansed and dried by gentle
patting with toilet tissue. Then a portion of the ointment or
cream is placed on a tissue and a thin film is gently spread over
the affected area. Products having a water-washable base are
easier to spread and remove after application and tend to stain
clothing less than products having an oleaginous base.
Rectal ointments and creams may be dispensed with special
perforated plastic tips for products to be administered into the
anus, primarily in the treatment of the pain and inflammation
associated with hemorrhoids. Before use, the rectal tip should
be thoroughly cleaned, screwed onto the ointment tube in place
of the cap, and lubricated with mineral oil or a lubricating jelly.
Anusol® and Tronolane® are examples of rectal ointments used
in the treatment of hemorrhoids.
Aerosols
Although occassionally used rectally, these are not generally
suitable for compounding. Pharmaceutical aerosols are pressurized
dosage forms containing one or more active ingredients
which upon actuation emit a fine dispersion of liquid and/or
solid materials in a gaseous medium. Pharmaceutical aerosols
are similar to other dosage forms because they require the same
types of considerations with respect to formulation, product stability,
and therapeutic efficacy. However, they differ from most
other dosage forms in their dependence upon the function of the
container, its valve assembly, and an added component—the
propellant—for the physical delivery of the medication in proper
form.
Aerosol products may be designed to expel their contents as a
fine mist, a coarse, wet or a dry spray, a steady stream, or as a
stable or a fast-breaking rectal foam. The physical form selected
for a given aerosol is based on the intended use of that product.
Rectal Aerosols
Rectal aerosol foams are commercially available containing antiinflammatory
agents. The aerosol package contains an inserter
device used to direct the foam when activated. The foams are
generally oil-in-water emulsions, resembling light creams.
Some available commercial preparations of rectal foams use rectal
inserters for the presentation of the foam to the anal canal.
Products such as ProctoFoam® (pramoxine hydrochloride) and
Proctofoam®-HC (with hydrocortisone) are used to relieve
inflammatory anorectal disorders. These products are accompanied
by applicators to facilitate administration. When ready to
use, the applicator is attached to the aerosol container and filled
with a measured dose of product. The applicator is then inserted
into the anus and the product delivered by pushing the
plunger of the applicator. After removal, the applicator and the
patient’s hands should be thoroughly washed.
COMPOUNDING FORMULAS
ENEMAS/MICROENEMASSOLUTIONS/
SUSPENSIONS/EMULSIONS
Diazepam 5 mg/mL Rectal Microenema
Diazepam 500 mg
Ethanol 95% 10 mL
Benzoic acid 0.1 gm
Sodium benzoate 4.9 gm
Benzyl alcohol 1.5 mL
Propylene glycol 40 mL
Hydroxypropyl methylcellulose 4.2 gm
Purified water qs 100 mL
Mix the ethanol, propylene glycol and benzyl alcohol together.
Add the diazepam and mix until dissolved. Add the hydroxypropyl
methylcellulose and mix until dispersed well. Mix the
sodium benzoate and benzoic acid in about 40 mL of purified
water. Slowly, add this mixture to the propylene glycol mixture
and mix well. Add sufficient purified water to volume, mix well,
and allow to stand until the solution is thickened. Package and
label.
Incorporate the micronized hydrocortisone into the methylcellulose
solution and mix well. Add sufficient preserved water to
volume and mix well. Package and label.
Wet the povidone with about 15 mL of water to form a paste. Use
a magnetic stirrer and add about 60 mL of water, stirring until a
clear solution is obtained. Add the micronized progesterone and
mix well. Add the remaining water to volume and thoroughly
mix. Package and label.
Dissolve the short-chain fatty acids and sodium chloride in about
90 mL of the purified water. Check and adjust the pH if necessary
using either 10% sodium hydroxide solution or 10% hydrochloric
acid to a pH between 7 and 8. Add sufficient purified water to volume
and mix well. Package and label.
Dissolve the monobasic and dibasic sodium phosphate in sufficient
purified water to volume. Package and label.
Mix the sulfasalazine with the glycerin to form a smooth paste.
Geometrically, incorporate the methylcellulose 2% solution to volume
and mix well. Package and label.
GELS
Combine the diltiazem hydrochloride with the propylene glycol
and mix to form a smooth paste. Incorporate the
hydroxyethylcellulose and mix well. Heat the preserved
water to about 70° C and slowly incorporate into the propylene
glycol mixture and mix well. Package and label.
Combine the nifedipine with the diethylene glycol monoethyl
ether to form a smooth paste. Add the lecithin:isopropyl
palmitate solution and mix well. Add sufficient Pluronic F-
127 20% gel to volume and mix thoroughly, using a
mechanical shearing force. Package and label.
Disperse the methylcellulose in 40 mL of hot (80–90° C) water.
Chill overnight in a refrigerator to effect solution. Disperse
the Carbopol 934 in 20 mL water. Adjust the pH of the dispersion
to 7.0 by adding sufficient 1% sodium hydroxide
solution (about 12 mL is required) and bring the volume to
40 mL with purified water. Dissolve the methylparaben in the
propylene glycol. Mix the methylcellulose, Carbopol 934 and
propylene glycol fractions using caution to avoid incorporating
air. Package and label.
OINTMENTS
Mix the anhydous lanolin with the white petrolatum.
Geometrically, incorporate the lanolin-white petrolaum mixture
into the nitroglycerin 2% ointment and mix until
uniform. Package and label.
REFERENCES
1. Readldon N, Ragazzi E, Ragazzi E. Effect of drug solubility
on the in vitro availability rate from suppositories with
lipophilic excipients. Pharmazie. 2000 May;55(5):372-7.
Sodium Phosphate Enema Solution
Sodium phosphate, dibasic, anhydrous 19 g
Sodium phosphate, monobasic, anhydrous 7 g
Purified water qs 118 mL
Sulfasalazine Enema
Sulfasalazine 3 g
Glycerin 5 mL
Methylcellulose 2% solution qs 50 mL
Diltiazem Hydrochloride 2% Gel
Diltiazem hydrochloride 2 g
Propylene glycol 10 mL
Hydroxyethylcellulose 2 g
Preserved water qs 100 mL
Nifedipine Gel 160 mg/mL in PLO
Nifedipine 16 g
Diethylene glycol monoethyl ether 10 mL
Lecithin:isopropyl palmitate solution 20 mL
Pluronic F-127 20% gel qs 100 mL
Rectal Lubricating Jelly Formula
Methylcellulose, 4000 cps 0.8 gm
Carbopol 934 0.24 gm
Propylene glycol 16.7 mL
Methylparaben 0.015 gm
Sodium hydroxide, qs ad pH 7
Purified water, qs ad 100 gm
Nitroglycerin 0.2% Ointment
Nitroglycerin 2% ointment 10 g
Lanolin, anhydrous 30 g
White petrolatum 60 g
Hydrocortisone 100 mg Enema
Hydrocortisone, micronized 100 mg
Methylcellulose 2% solution 25 mL
Preserved water qs 50 mL
Progesterone 200 mg per 100 mL Enema
Progesterone, micronized 200 mg
Povidone 10 g
Purified water qs 100 mL
Short Chain Fatty Acid Enema
Sodium acetate, trihydrate 817 mg
Sodium propionate 288 mg
Sodium butyrate 440 mg
Sodium chloride 82 mg
Purified water qs 100 mL
7. Which of the following characteristics may help in increasing the rate of drug
absorption?
I. insoluble in the vehicle
II. soluble in rectal fluids
III. very viscous vehicle
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
8. How can viscosity affect a rectal dosage form?
I. If too high, drug release may be slow
II. Is needed to help ensure uniformity of suspensions during preparation
III. Helps minimize degradation of the drug
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
9. Which of the following ingredients are commonly used intrarectally and
around the rectal opening?
A. bismuth subnitrate
B. diazepam
C. hydrocortisone
D. progesterone
E. methotrexate
10.Microenemas generally consist of the drug in a volume of about:
A. 1-5 mL
B. 5-10 mL
C. 10-15 mL
D. 15-25 mL
E. 25-50 mL
11. My practice setting is:
A. Community-based C. Hospital-based
B. Managed care-based D. Consultant and other
12. The quality of the information presented in this article was:
A. Excellent B. Good C. Fair D. Poor
13. The test questions correspond well with the information presented.
A. Yes B. No
14. Approximately how long did it take you to read the Secundum Artem
article AND respond to the test questions?
15. What topics would you like to see in future issues of Secundum Artem?
1. When administered rectally, at least what percent of the active ingredients will
avoid the first-pass effect?
A. Less than 10%
B. 10-25%
C. 25-50%
D. 50-70%
E. More than 70%
2. Which of the following factors can affect the efficacy of a rectally administered
dosage form?
I. whether the drug is an ester, salt, or complex
II. the presence of adjuvants in the formula
III. the particle size of the drug
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
3. Generally, it is best to keep water out of a fatty acid base suppository rectal
dosage form because:
I. it may accelerate oxidation of fat
II. it may increase the degradation rate of drugs
III. it may support bacterial/fungal growth
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
4. Microenemas can be easily prepared by adding what ingredient to an injection?
A. buffering agent
B. chelating agent
C. preservative
D. surfactant
E. thickening agent
5. Alginic acid, carbomer, cetostearyl alcohol, hydroxypropyl cellulose,
magnesium alminum silicate and povidone are all agents that can be used as:
A. buffering agents
B. chelating agents
C. preservatives
D. surfactants
E. gelling agents
6. Which of the following dosage forms can be used to produce a systemic effect
of an active drug?
A. rectal enema
B. rectal gel
C. rectal ointment
D. rectal microenema
E. all the above