Rectal ROA

Obj. 1

Define rectal drug delivery

Administration of API + excipients (pharmaceutical preparations) via RECTUM for local or systemic effect.

Obj. 2

Enlist 3 types of dosage forms delivered via rectal route.

1. SOLID: Suppository

2. LIQUID: Enema

3. SEMI-SOLID: Ointment, Cream

Obj. 3

Discuss therapeutic application of rectal route.

• Rectal Diseases (Perianal Abscess, hemorrhoids)

• Ex:

  • Steroids

  • Anti-inflammatory drugs

  • Anti-cancer drugs

  • NSAIDs

Obj. 5 (obj. 4 - FYI)

Explain rectal route.

• Rectum - last (usually empty), portion of the large intestine located above the anal canal

• Drugs can easily be introduces, retained and absorbed

• SA absorbing of the rectum is smaller (than small intestine b/c lack of villi + micro-villi)

• Rectal route = Enteral route

Obj. 6

Is rectal route local & systemic?

Yes

Obj. 7

How can Systemic delivery be useful via rectal route?

Systemic Delivery can be useful for drugs with:

• Limited absorption in upper GI tract

• Unstable to proteolytic enzymes

• ⬆ High hepatic 1st-pass effect

• Irritation to Gastric mucosa

• Need ⬆ high doses & CANNOT easily be formulated in oral solid dosage forms

Obj. 8

Advantages & Disadvantages of rectal drug delivery.

• What are the Advantages of rectal drug delivery?

Advantages

1. Rectal ROA is 2nd choice (oral + IV = 1st choice)

2. Becomes 1st choice in certain conditions (N/V, objectionable taste, unconsciousness during post-operative treatments, swallow difficulties - Dysphagia, inflammation @ site of intra-muscular administration)

Obj. 8

Advantages & Disadvantages of rectal drug delivery.

• What are the Disadvantages of rectal drug delivery?

Disadvantages

1. Neglected due to erratic (variable) absorption

2. Dissolution problems due to small fluid content of the rectum

3. Limited Absorption SA

4. Drug metabolism (=> metabolized by 1st-pass effect)

5. Poor patient compliance

Obj. 9

Mechanism of Drug absorption through rectal route.

• Epithelia in rectum → abilities to absorb drugs.

• SA is small b/c w/out villi and microvilli (but larger than nasal and buccal absorptive surfaces).

• Rectal region is also extensively drained by the lymphatic circulation and could increase the systemic absorption of some highly lipophilic drugs.

• Empty rectum provides a constant and static environment as compared to the upper gastrointestinal tract.

• LOWER RECTUM is drained by the lower and middle hemorrhoidal veins and bypasses the liver, avoiding hepatic first pass effect and allowing drugs to exert systemic effect prior to metabolism in the liver.

• Drugs delivered through to the lower and middle hemorrhoid veins are absorbed rapidly and effectively.

• Middle and lower hemorrhoid veins enter systemic circulation because they bypass the liver.

• Superior hemorrhoidal vein drains into the portal system, therefore metabolized by hepatic portal system (first pass effect)

• Process of absorption is passive diffusion.

• Rectal dosage forms should be inserted in the LOWER part of the RECTUM to avoid the absorption of the drug by the upper hemorrhoidal vein which supplies blood to the portal vein.

Obj. 10

What are the 4 factors that affects rectal drug delivery?

1. Drug

2. Formulation

3. Pathology

4. Physiology