Page 1: Introduction to Rectal Drug Delivery Systems

• Overview of rectal drug delivery systems.

• Importance of systemic absorption and bypassing first-pass metabolism.

• Key term: Hepatic portal vein.

Page 2: Learning Objectives

• Physiology of the Rectal Cavity: Understand the anatomical features.

• Physiological Challenges: Identify barriers to effective drug delivery.

• Ideal Properties: Physicochemical properties needed for rectal drug delivery systems (DDS).

• Formulation Factors: Components affecting formulation success in rectal DDS.

• Types of Rectal DDS: Different formulations available.

• Patient Conditions: Situations where rectal administration is beneficial.

Page 3: Applications of Rectal DDS

• Local Applications:

  • Hemorrhoids: Treatment using vasoconstrictors.

  • Local infections: Use of antibiotics.

  • Constipation: Administration of laxatives and enemas.

• Systemic Applications:

  • Situations like unresponsive patients (vomiting, seizures).

  • Drugs unstable in the gastrointestinal tract.

  • Drugs that irritate the gastrointestinal tract.

Page 4: Advantages and Disadvantages of Rectal DDS

• Advantages:

  • Useful for both local and systemic effects.

  • Bypasses first-pass metabolism.

  • Beneficial for patients unable or unwilling to take oral medications.

• Disadvantages:

  • Variable bioavailability due to factors like fecal presence.

  • Patient compliance issues: generally unpopular.

  • Low absorption rates and administration difficulties.

  • Retention time challenges and potential local side effects.

Page 5: Physiology of the Rectal Cavity

• Importance of dosage form placement within the rectal cavity for effective drug action.

Page 6: Physiological Barriers for Rectal DDS

• Volume: Approximately 3mL for effective delivery.

• pH Levels: Adults (7.0-8.0), Children (7.2-12.1) with minimal buffering capacity.

• Vascularization: Significance of the superior rectal vein and first-pass effect.

• Anatomy Considerations: Length of rectum (10-15 cm) and circumference (15-35 cm).

• Anal sphincter critical for dosage retention.

Page 7: Ideal Physicochemical Properties for Rectal DDS

• Molecular Weight: Low molecular weight (<1,000 Da) ideal for absorption.

• Partition Coefficient: Log K_o/w should be between 1 to 3 for optimization.

• Dissociation Constant (pKa): Influences unionized species at rectal pH (7).

Page 8: Ideal Formulation Factors for Rectal DDS

• Particle Size: Affects dissolution rates and absorption.

• Vehicle Choice:

  • Liquids: Faster onset of action.

  • Solids: Longer drug duration.

• pH: Maintain around 7 to reduce irritation and evacuation triggers.

• Volume of Administration: Should be a few mL for effective delivery.

Page 9: Examples of Rectal DDS

• Forms Include:

  • Suppositories.

  • Rectal enemas.

  • Rectal gels and foams.

  • Ointments and creams.

Page 10: Interaction with the Macy Catheter

• Questions about the Macy Catheter:

  1. Potential uses.

  2. Facilitates quick symptom management in compromised patients.

  3. Aseptic technique requirements during insertion.

  4. Purpose of the balloon and its filling material.

Page 11: Suppository Bases

• Oleaginous Bases:

  • Properties: soothing, may stain, melt upon temperature.

  • Examples: Cocoa butter, Fattibase™, Witepsol®, MBK™.

• Water Soluble Bases:

  • Properties: non-staining, can irritate, dissolve quickly.

  • Examples: PEGs, glycerinated gelatin.

Page 12: Case Study - Cafergot® Suppositories

• Composition:

  • Contains ergotamine tartrate and caffeine.

  • Dosage: 2mg/100mg.

• Indications: Used for migraine treatment.

• Excipients: Cocoa butter and tartaric acid.

• Special Packaging: Sealed in foil to prevent leakage; chilling required if softening occurs.

Page 13: Suppository Administration Guidelines

• Insertion Technique:

  • Pointed end first, insert until it passes the rectal sphincter.

  • Depth of insertion: 1/2 - 1 inch for infants, ~1 inch for adults.

Page 14: Rectal DDS Formulations

• Formulation Examples:

  • Suppositories: Solid bases with drug dissolved or dispersed.

  • Rectal Enemas: Solutions or suspensions that require longer retention.

  • Rectal Gels & Foams: Applied with applicators, sometimes messy.

• Device Considerations:

  • Use a finger cot or glove for hygiene.

Page 15: Depth of Application for Rectal DDS

• Application Targets:

  • Suppositories: Rectal region.

  • Foams: Sigmoid colon.

  • Enemas: Descending colon.

Page 16: Lecture Quiz Questions

• Evaluate understanding of rectal dosage forms:

  1. Reasons for variable bioavailability.

  2. Key formulation factors for rectal drug delivery.

  3. Ideal base selection for fast release of hydrophobic drugs in suppositories.

Page 17: Recap Learning Objectives

• Goals:

  1. Describe the physiology of the rectal cavity.

  2. Explore physiological challenges to drug delivery.

  3. Identify ideal physicochemical properties for rectal DDS.

  4. Recognize formulation factors for rectal DDS.

  5. Review different types of rectal DDS.

  6. Identify patient conditions benefitting from the rectal route.