Pharmacology: Suppositories and Rectal Absorption

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.