Pharmacology: Suppositories and Rectal Absorption

Questions and Answers

What is the characteristic melting point of the most stable polymorph of cocoa butter?

34 to 35°C (correct)

18°C

28 to 31°C

22°C

What is the primary reason for the poor performance of cocoa butter in high-speed manufacturing?

Insufficient contraction at cooling (correct)

High softening point

High melting point variability

Poor water solubility

Which of the following conditions is crucial for the formation of the desired ß form of cocoa butter?

Using α seed crystals

Maintaining a temperature above 34.5°C

Cooling rapidly after heating

Keeping ß form present while heating (correct)

What ingredient in glycerinated gelatin acts as a hygroscopic element that must be protected from water?

Glycerin Signup and view all the answers

Which factor is NOT a disadvantage of cocoa butter?

High melting point Signup and view all the answers

What is the primary blood supply to the rectum?

Superior rectal artery Signup and view all the answers

Which of the following factors is least likely to affect drug absorption when administered rectally?

Presence of villi in the rectal wall Signup and view all the answers

How does the blood flow from the middle hemorrhoidal vein impact drug absorption?

It bypasses the liver and enters general circulation Signup and view all the answers

What is the average volume of inert mucous fluid contained in an empty rectum?

2-3 mL Signup and view all the answers

Which physicochemical factor does NOT influence rectal drug absorption?

Drug’s color and appearance Signup and view all the answers

Study Notes

Suppositories and Routes of Administration

Common usage areas include rectum, vagina, and urethra.
Drug content in suppositories can range from 0.1% to 40%.

Factors Affecting Rectal Absorption

Dosage can differ between rectal and oral administration.
Physicochemical Factors:
- Lipid-water solubility, particle size, and nature of the base affect absorption.
Physiological Factors:
- Colonic content, pH, buffer capacity, circulation route, and specific rectal site impact absorption.

Physiology of the Rectum

Rectum constitutes the terminal 15-20 cm of the large intestine.
Lacks villi and has a flat wall surface with a one-cell-layer-thick epithelium that secretes mucus.
Average rectal contents include 2-3 mL of inert mucus, with a surface area of approximately 300 cm².
Rectal fluid pH is around 7.5, lacking buffering capacity.

Rectal Blood Circulation

Superior rectal artery supplies blood; drainage via superior, middle, and inferior hemorrhoidal veins.
Middle and inferior hemorrhoidal veins allow drugs to enter general circulation directly, bypassing the liver.
Superior hemorrhoidal vein drains blood into the hepatic portal, directing drugs through the liver.

Cocoa Butter Polymorphs

Cocoa butter has four forms with varying melting points:
- α form: 22°C
- γ form: 18°C
- ß' form: 28 to 31°C
- ß form: 34 to 35°C (most stable).
Transition to ß form requires specific heating and seed crystals.

Cocoa Butter Compounding

Maintain heating below 34.5°C to ensure stability and release.
Disadvantages include low softening point and poor water absorptive properties.
Alternatives to cocoa butter include vegetable oils, waxes, triglycerides, and fatty alcohols.

Water-Soluble and Water-Miscible Bases

These bases may cause irritation due to water uptake.
Example: Glycerinated gelatin consists of glycerin and gelatin, and is hygroscopic.
Example: Polyethylene glycol (PEG) varies by molecular weight, contributing to its properties.

Compressed Tablets

Not commonly used for rectal suppositories but gaining popularity for vaginal applications.
Advantages include easier manufacturing and greater stability.

Formulation Considerations

Important formulation factors: composition, melting behavior, rheological properties, onset of action, and application area.
Local absorption is critical for effectiveness, while systemic absorption requires careful consideration to avoid erratic effects.

Preparation of Suppositories

Hand rolling and shaping require cocoa butter and are an older method.
Cold compression suitable for heat-sensitive ingredients.
Molding from a melt is the most popular method involving heating and equipment.

Molding from a Melt Procedure

Heat base materials, mix with active ingredients, pour into molds, and cool.
Considerations include mold type, lubrication, and accurate volume measurement.

Calibration of Molds

Molds must be clean and dry prior to use.
Weight average of produced suppositories determines specific calibrations for future batches.

Suppository Molding Tips

Use overage in batch preparation to account for loss.
Avoid refrigeration of molds before use and slightly overfill cavities for cooling contraction.

Calculations for Suppositories

Minimal volume impact of active drugs (<100 mg) in a 2 g suppository.
Required density factors for proper ingredient weight calculations; if unknown, can be calculated by base weight ratio.

Description

Explore the pharmacological aspects of suppositories and their administration routes, focusing on rectal absorption. This quiz delves into the factors affecting drug absorption, the anatomy of the rectum, and its unique circulatory characteristics. Test your knowledge on these critical pharmacological concepts.