(4A) Suppositories: Rectal and Vaginal Delivery Systems

SUPPOSITORIES

Definition

Solid dosage forms containing drug

SUPPOSITORIES

• Inserted into

• Rectum

• Vaginal cavity

• Urethra

 SUPPOSITORIES

• After insertion:

• Melt OR dissolve → release drug

DRUG RELEASE MECHANISMS - overview

1. Melting mechanism (Oleaginous base)

2. Dissolution mechanism (Water-soluble base)

1. Melting mechanism (Oleaginous base)

• Example: Cocoa butter (Theobroma oil)

• Solid at room temp → melts at body temp (~37°C)

• Drug released from melted base

 Melting mechanism (Oleaginous base)

Key concept:

• Hydrophilic drug → releases FAST

• Lipophilic drug → releases SLOW (stays in oily base)

2. Dissolution mechanism (Water-soluble base)

• Example: PEG (polyethylene glycol)

• Does NOT melt → dissolves in body fluids

• Drug diffuses out

Partition Theory

• Drugs = weak acids or bases

• Ionized → water soluble → poor membrane absorption

• Unionized → lipid soluble → GOOD membrane absorption

Membranes are lipid →

only unionized drugs cross easily

TYPES OF SUPPOSITORIES - chart

Type	Shape	Weight	Notes
Rectal	Cylindrical, tapered	Adult ~2 g, Infant ~1 g	Most common
Vaginal (Pessaries)	Oval/cone	3–5 g	Larger
Urethral (Bougies)	Pencil-shaped	Thin (4–5 mm)	Very small

ADVANTAGES (RECTAL ROUTE) - overview

• Cannot take oral:

• Avoids:

• Useful for:

ADVANTAGES (RECTAL ROUTE)

• Cannot take oral:

• Vomiting

• Unconscious

• Seizures (kids)

• Post-op

ADVANTAGES (RECTAL ROUTE)

• Avoids:

• GI irritation

• Drug destruction in stomach

• First-pass metabolism (PARTIALLY)

ADVANTAGES (RECTAL ROUTE)

• Useful for:

• Young, elderly, mentally ill

DISADVANTAGES (RECTAL ROUTE)

• Slow/incomplete absorption

• Variable between patients

• Local irritation

• Storage issues (melting risk)

• Hard for large-scale production

THERAPEUTIC USES (RECTAL ROUTE)

• Local:

  • Constipation

  • Hemorrhoids

• Systemic:

  • Analgesics

  • Sedatives

  • Antiepileptics

FACTORS AFFECTING DRUG ABSORPTION

1. Physiological Factors

2. Drug Factors

3. Base Factors

FACTORS AFFECTING DRUG ABSORPTION

Physiological Factors - overview

Rectum facts:

Fecal content

Circulation

pH & Buffering

FACTORS AFFECTING DRUG ABSORPTION

Physiological Factors - Rectum facts:

• Length: 5–20 cm

• Fluid: 2–3 mL mucous

• No villi → less absorption surface

FACTORS AFFECTING DRUG ABSORPTION

Physiological Factors -  Fecal content

• Feces ↓ drug absorption

• Must remove before use:

  • Enema recommended

FACTORS AFFECTING DRUG ABSORPTION

Physiological Factors -   Circulation

• Lower rectum → bypass liver → systemic

• Upper rectum → goes to liver → first-pass metabolism

👉 Placement matters!

FACTORS AFFECTING DRUG ABSORPTION

Physiological Factors -    pH & Buffering

• pH: 7–8 (neutral)

• NO buffering capacity

👉 pH affects ionization → affects absorption

FACTORS AFFECTING DRUG ABSORPTION

 Drug Factors - overview

Partition coefficient

Ionization

Concentration

Other:

• Particle size

• Diffusion rate

• Surfactants

 

FACTORS AFFECTING DRUG ABSORPTION

 Drug Factors - Partition coefficient

• Lipophilic drug + fatty base → poor release

• Water-soluble drugs → better release from fatty base

FACTORS AFFECTING DRUG ABSORPTION

 Drug Factors - Ionization

Unionized → better absorption

FACTORS AFFECTING DRUG ABSORPTION

 Drug Factors - Concentration

Above certain level → no further increase in absorption

FACTORS AFFECTING DRUG ABSORPTION

 Base Factors

• Melting point

• Solubility

• Compatibility

POLYMORPHISM (VERY IMPORTANT)

Definition:

Same drug → different crystal forms

POLYMORPHISM (VERY IMPORTANT)

Why it matters:

• Different forms → different:

  • Melting point

  • Stability

  • Drug release

POLYMORPHISM (VERY IMPORTANT)

 Example

Cocoa Butter

• Different forms:

  • Melt <37°C → melts too early (leaks)

  • Melt >37°C → won’t melt in body

• Must control heating

 

IDEAL SUPPOSITORY BASE

• Melts at body temp (~37°C)

• Non-irritating

• Stable

• Easy to handle

• No leakage

• Compatible with drugs

• No polymorphism issues

TYPES OF BASES - overview

1. Oleaginous (Fatty)

2. Water-Soluble

3. Water-dispersible

TYPES OF BASES - Oleaginous (Fatty)

• Cocoa butter

• Melts at body temp

TYPES OF BASES - Oleaginous (Fatty)

Pros:

• Non-irritating

• Easy melting

TYPES OF BASES - Oleaginous (Fatty)

cons-

• Polymorphism

• Low melting point in hot climates

• Poor water absorption

TYPES OF BASES - Water-Soluble

types

a. Glycerinated gelatin

• Hygroscopic

b. PEG (VERY IMPORTANT)

• Dissolves (does NOT melt)

• Adjustable properties by mixing MWs

TYPES OF BASES - Water-dispersible

Hybrid systems

MANUFACTURING METHODS - overview

1. Hand molding

2. Compression molding

3. Pour molding (MOST COMMON)

4. Automatic molding

MANUFACTURING METHODS - Hand molding

• Small scale

• Cocoa butter

MANUFACTURING METHODS -  Compression molding

Uses pressure

MANUFACTURING METHODS -  Pour molding (MOST COMMON)

1. Melt base

2. Add drug

3. Pour into mold

4. Cool

MANUFACTURING METHODS - Automatic molding

Industrial