Suppositories

• Mucosal membrane:
  • Epithelium cells: Cylindrical cells and Goblet cells
• Large surface area for absorption (» 300 cm2)
• Moist surface (covered in mucus [» 3 mL])
• Neutral pH (» 7.5)
• Excellent blood supply
• Absence of potentially destructive enzymes
• Suitable for delivery of locally and systemically acting medicaments

The vehicle for drug delivery is a base - either an oleaginous fatty base or a water-miscible base

Physiological vehicle characteristics:

Physicochemical vehicle characteristics:

Drug release from suppositories:

• Difficult to achieve due to the low volume of water present (3mL)
• During vehicle dissolution water is absorbed - this sensation can induce pain for the patient
• As the suppository structure breaks down, dissolved drugs begin to migrate towards the mucosal membranes (concentration gradient)
• Dispersed drugs (i.e. suspensions of water immiscible drug) leave the base via motility or gravitational effects
• Upon reaching the mucosal membrane drug must first dissolve in the mucosal fluid before the process of absorption can take place:
  • Diffusion through the mucus layer
  • Passive transport across the epithelium

Advantages

• Exerts a local effect on the rectal mucosa

• For an anaesthetic effect

• Promotes evacuation of the bowel

• Avoidance of GIT irritation –some drugs can irritate the GIT

• Used for patients who are unconscious or vomiting

• Avoids first pass metabolism

• Rapid onset of action due to the large blood supply

Disadvantages

• May be unacceptable to certain patients, e.g. cultural sensitivities

• May be difficult to self-administer –arthritic or physically compromised patients

• Unpredictable and variable absorption in vivo

Suppository moulds are calibrated for the weight of Theobroma Oil BP

Some synthetic fats have the same density as Theobroma Oil BP - Recalibration not required

Recalibration of moulds is required if the base is not Theobroma Oil BP

• Prepare a number of suppositories containing only the base
• Weigh the suppositories and divide by number of suppositories
• Weight of each suppository equals the Mould Calibration