2. S.N Contents
1 Introduction
2 Advantages & Disadvantages
3 Applications
4 Factors affecting rectal drug absorption
5 Anatomy and Physiology of Rectum
6 Absorption Barriers
7 Absorption from Rectum
8 Rectal Dosage Forms
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3. INTRODUCTION
Rectal drug delivery system means administration of drug
or pharmaceutical preparation via rectum using a
mucoadhesive polymer for local or systemic effect.
Different types of rectal dosage forms –
1. Solid dosage forms- Suppositories.
2. Liquid dosage forms- Enemas, solutions and
suspensions.
3. Semisolid dosage forms-Ointments, creams and
gels(hydrogels).
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4. ADVANTAGES
1. Useful for infants ,children and unconscious patients
who have difficulty in swallowing oral medicine.
2. Avoiding first pass metabolism e.g. lidocaine , morphine.
3. In case of nausea and vomiting.
4. Contact of drug with digestive fluid is avoided e.g.
Penicillin, vitamins.
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5. 5. Drugs which causes gastric irritation or ulceration can be
avoided by giving drug via this route e.g. aspirin, naproxen.
6. Drug absorption may be easily discontinued in case of
accidental overdose.
7. Drugs administered per rectum have a faster action than
via the oral route and a higher bio-availability.
8. When oral intake is restricted such as prior to X-ray
studies , prior to surgery or in patients having upper GIT
disease.
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6. DISADVANTAGES
1. Many drugs are poorly or erratically absorbed across the
rectal mucosa.
2. Dissolution problem due to small fluid content of the
rectum.
3. They are inconvenient and not preferred by patients.
4. Development of proctitis i.e. inflammation of rectum.
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7. APPLICATIONS
A. For local effect:
• In case of itching, pain and hemorrhoids.
• Locally active drugs includes astringents, local
anesthetics, antiseptics , vasoconstrictors, anti-
inflammatory drugs, soothing and protective agents and
laxatives.
B. For systemic effects:
• Anti- asthmatic, anti- rheumatics, analgesics.
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8. ANATOMY AND PHYSIOLOGY OF
RECTUM
• Rectum is a hollow organ that comprises of the last
portion of large intestine and is about 15-20 cm long
and 1.5-2 cm width without any villi.
• Rectal wall is formed by an epithelium which is one
cell layer thick and composed of cylindrical cells
and goblet cells which secrete mucus.
• The surface area available for drug absorption in
the rectum is approximately 200-400 cm2 .
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9. • Volume of fluid in rectum is about 1-3 ml and is
viscous with a pH of about 7.5-8.
• Rectal tissues are drained by superior, middle and
inferior hemorrhoidal veins but only the superior vein
connects with the hepatic-portal system.
• Absorption of drugs takes place mainly by passive
diffusion.
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10. Absorption from rectum
3 veins
Superior
hemorrhoidal
vein
Middle
hemorrhoidal
vein
Inferior
hemorrhoida
l vein
Drains into hepatic-
portal system
Drains into systemic
circulation
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15. Absorption Barriers
a) Mucus layer-
• The mucus layer adjacent to the colonic mucosa
acts as a diffusion barrier.
• Mucus production in the colon is a function of
goblet cells and as the proportion of goblet cells
increases with age, this may be a factor that
changes.
• The mucus layer may also be affected by disease
and is thinned by the action of prostaglandins
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16. b) Movable water layer-
• The center of the colonic lumen to the mucosa
passes through regions of decreasing mixing.
• At the mucosal surface there is a layer of relatively
unstirred water.
• All molecules must pass through this area by
diffusion.
• Some viscous soluble dietary fibers may increase
the thickness of this layer by reducing intra luminal
mixing.
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17. c) Chemical barriers-
• Some dietary fibers such as pectin and
chitosan have cation-exchange properties
which may bind charged molecules such as
bile acids.
• Drug molecules could be trapped within the
solid matrix of the concentrated dietary
residue or within the entangled chains of a
soluble dietary fiber.
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18. Factors affecting rectal drug
absorption
A] Physiological factors-
1. Quantity of dissolution fluid available-
• Very small volume of fluid (3ml) is present under
normal conditions.
• Only under non-physiological (diseased) conditions
this volume is enlarged.
• Hence absorption of slightly soluble drugs would be
dissolution rate limited. E.g. Phenytoin.
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19. 2. Properties of rectal mucus-
• Properties such as composition, viscosity,
surface tension, pH have great influence on drug
bioavailability.
3. Colonic content-
• Drug absorption would be higher when the
rectum is empty.
4. Motility of rectal wall-
• When the body is upright, the abdominal organs
press on to the rectum which stimulates
spreading and promotes absorption.
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20. • Motility of the muscle of rectal wall also helps in
increasing absorption.
B] Physicochemical factors-
1. Solubility-
Higher the solubility, higher is the dissolution
rate, higher will be the absorption.
2. Degree of ionization-
At alkaline pH of rectal mucosa, basic drugs will be
in unionized form and hence will get readily
absorbed.
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21. 3. Particle size-
Smaller the size, better is the dissolution and hence
better is the absorption. Ideal particle size should be
50-100µm.
4. pH-
Rectal mucosal pH is slightly alkaline (7-8) hence
basic drugs are absorbed faster than acidic drugs.
5. Partition coefficient-
Higher the partition coefficient, higher is the
absorption of the drug.
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22. Rectal Dosage Forms
1. Suppositories-
It is a small medicated cone-shaped mass which is
inserted into the rectum where it melts at body temperature
and releases the medicament.
They are 1g for children and 2.5g for adults.
Lipophilic drugs are usually incorporated into water- soluble
bases while hydrophilic drugs are formulated into the fatty
base suppositories.
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24. Suppository Bases
Fatty bases-Cocoa Butter; Hard Butter; Witepsol
Water soluble bases- PEG; Tween 61
Evaluation Parameters
Finished suppositories are routinely inspected for:
Appearance
Content uniformity
Melting range test
Drug release test
Fragility test
Disintegration test
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25. Case study 1
Yahagi R et.al., Int J Pharm
They have prepared mucoadhesive
suppositories of ramosetron HCl using carbopol.
The viscosity of suppository base and
Ramosetron release properties were examined.
The base viscosity increased with the addition
of carbopol.
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26. Case study 2
Remeth J Dias et.al.
They have prepared mucoadhesive microsphere
based suppository containing granisetron HCl for
management of emesis in chemotherapy.
Suppositories of microspheres were formulated
by fusion method using hydrophilic and lipophilic
polymer base.
Polymers used: Xanthum gum, PEG, HPMC,
Cocoa butter, Sodium alginate.
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27. 2. Enemas-
It is a procedure of introducing liquid into
rectum and colon via anus.
Types-
a) Evacuant enema-
Used as bowel stimulant to treat constipation. E.g.
Sodium phosphate, MgSO4 enema.
Volume of evacuant enema may reach up to 2 L.
They should be warmed to body temperature before
administration.
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28. b) Retention enema-
Its volume doesn’t exceed 100 ml.
No warming is needed before administration.
Eg: Hydrocortisone
It may exert-
1. Local effect- Barium sulfate enema used as radio
opaque contrast media.
2. Systemic effect- nutrient enema containing
carbohydrates, vitamins & minerals.
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29. 3. Rectal aerosols-
Rectal aerosols or foam products
are accompanied by an applicator to
facilitate administration. The applicator is
attached to the container and filled with the
measured dose of the product.
Metered dose aerosols are also available.
Applicator is inserted into the anus and
plunger is pushed to deliver drug into the
rectum.
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31. 4.Other Rectal Semisolids:
Rectal Cream, Gels and Ointments:-
These preparations are used for topical
application to the perianal area for insertion
within the anal canal. They largely are used to
treat local conditions of anorectal pruritus,
inflammation and the pain and discomfort
associated with hemorrhoids.
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32. The drugs includes astringents (Zinc oxide),
protectants and lubricants (Cocoa butter, lanolin),
local anesthetics (Pramoxine HCL), and antipruritic
and anti inflammatory agents(Hydrocortisone).
• Packaging: rectal ointments, creams and gels are
packed with special perforated plastic tips for
products to be administered in to the anus.
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33. Case study 1
Mucoadhesive chitosan hydrogels
Marta Cerruti et.al., Acta Biomaterialia.
To treat ulcerative colitis.
Mucoadhesive drug delivery systems stick to mucosal tissues and
prolong the local retention time of drugs.
A mucoadhesive hydrogel is proposed to improve the efficacy of
rectal sulfasalazine (SSZ) administration.
The gel is made of catechol modified-chitosan(CAT-CS)
crosslinked by genipin.
Compared to oral SSZ treatment, rectal SSZ/Cat-CS delivery was
more therapeutic and induced a lower plasma concentration of the
potentially sulfapyridine by-product.
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34. Case study 2
Koffi AA et.al. have created a mucoadhesive hydrogel of
quinine for rectal administration by using a thermosensitive gel
poloxamer 407 and a bioadhesive polymer HPMC.
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35. CONTROLLED RELEASE VIA RECTAL
ROUTE-
Controlled-release formulations are designed to release
the active agent in a sustained and controlled fashion.
Since the total acceptable size of a rectal formulation
significantly exceeds the size possible for oral formulations,
rectal administration for the purposes of controlled-release
offers a significant advantage.
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36. Case Study
L.G.J.de Leede et.al.
They have created rate controlled hydrogel
preparation of antipyrine or theophylline using
hydroxyethyl methacrylate (HEMA) and
ethylene glycol dimethacrylate(EGDMA) as
crosslinking agent.
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37. Conclusion
The volume of fluid present in rectum is very small which
hinders the absorption of drugs.
The rectal DDS offer patients an option that is less
invasive and the drug can be administered in
unconscious and pediatric patients.
Higher bioavailability can be obtained.
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38. References:
Ansel’s Pharmaceutical Dosage Forms and Drug
Delivery Systems, by Howard c. Ansel , Lloyd v.
Allen, Jr. Nicholas G. Popovich. 8th edition.
Rectal drug delivery , Wikipedia.
Images from Google images.
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