Pharmaceutics: Suppository Drug Absorption

Rectal Drug Absorption

• Drug dissolved in suppository diffuses out towards rectal membrane, followed by absorption
• Suspended drug leaves vehicle, precipitates or separates due to gravity and motility, then dissolves and diffuses before being absorbed

Physiological Factors Affecting Rectal Drug Absorption

• Properties of rectal fluid:
  • Composition, viscosity, pH, and surface tension affect drug bioavailability
• Content of the rectum:
  • Rectum is usually empty, but fecal contents from higher parts of the colon can affect absorption
• Enzymes:
  • Rectum has no active esterases or peptidases, unlike the GIT
• Volume of available fluids:
  • Typical volume of available fluid in the rectum is ~3 ml spread on a layer of ~100 µm thick
  • Volume increases under non-physiological conditions, affecting absorption of slightly soluble drugs
• Motility of the rectal wall:
  • Rectal wall exerts pressure on suppository, promoting spreading and absorption

Suppositories

• Intended to produce local action, systemic effect, or mechanical effect to facilitate emptying the lower bowel
• Prepared in various weights, sizes, and shapes according to intended use
• Drug is incorporated into a base, such as cocoa butter, glycerinated gelatin, or PEG

Formulation of Suppositories

• Pharmacist must consider shape, content, weight, and vehicle requirements
• Shape: cylindrical, conical, or torpedo
• Content: ranges from 0.1 to 40% w/w
• Weight: ranges from 1 to 4 grams
• Vehicle requirements:
  • Melts or dissolves in the rectum and mixes with rectal fluid at ~34-36°C
  • Melting range should be low enough to give rapid solidification and avoid drug precipitation

Fatty Bases

• Specifications:
  • Origin and chemical composition (entirely natural, synthetic, or modified natural)
  • Physical and chemical incompatibilities with additives (preservatives, antioxidants, emulsifiers)
• Melting range
• Solidification point
• Saponification value
• Iodine value
• Wetting and emulsifying properties
• Water number
• Acid value

Polymorphism of Cocoa Butter

• Exists in four polymorphic forms: α, β, β', and γ
• β polymorph is stable, while α, γ, and β' are unstable and revert to β
• To minimize formation of unstable forms, heat only briefly and below 36°C

Lowering of Melting Point

• Caused by addition of certain drugs (volatile oils, phenol, chloral hydrate)
• Can be raised back to desired range by adding beeswax or spermaceti (3-5% w/w)

Synthetic Fats vs Cocoa Butter

• Advantages of synthetic fats:
  • No polymorphism
  • Contain mainly saturated acids (iodine number < 3)
  • Melting range is usually about 3°C higher
  • Acid content is lower (mostly < 0.5)
  • Hydroxyl number (5-30)