Gastro-Retentive Drug Delivery System

Objectives of Gastro-Retentive Drug Delivery Systems

• Prolongs residence time of oral dosage forms in the stomach from hours to days.
• Delivers drugs locally in the stomach and upper small intestine, ideal for treating peptic ulcers.
• Enhances patient compliance through reduced dosing frequency.

Stomach Physiology and Function

• Composed of three compartments: Fundus, Body, Antrum.
• Fundus and Body serve as reservoirs for ingested materials; Fundus generates positive pressure to promote content movement.
• Antrum acts as a mixing site and drain pump to the duodenum.
• Stomach functions include food reservoir, processor, sterilizer, and delivery port to the intestine.

Gastric Motility

• Characterized by phases: Interdigestive Myoelectric Motor Complex (IMMC) occurs during fasting and varies during feeding.
• Fasted State Phases include:
  • Phase I: Basal state (45-60 min) with minimal contractions.
  • Phase II: Preburst state (30-45 min) with increased contraction frequency and strength.
  • Phase III: Burst state (5-15 min) clears out digested material, known as “Housekeeper waves.”
  • Phase IV: Brief non-contraction period (about 5 min).
• Fed State: Liquids empty within 30 min, solids depend on meal type, size, and density with emptying time of 2-6 hours.

Limitations of Gastro-Retentive Systems

• Not suitable in the fasted state due to the risk of rapid gastric emptying.
• Release rate influenced by the IMMC phase.
• Single-unit dosage forms may unpredictably empty all at once.
• Continuous food consumption needed to maintain gastric retention.

Factors Influencing Gastric Retention

• Density: Dosage forms with density <1 g/cm³ float; high-density forms sink, affecting retention.
• Size and Shape: Larger than 7 mm has better retention; irregular shapes enhance residence time.
• Food Intake: Viscosity, volume, caloric value, and frequency of meals impact retention.
• Demographics: Females and elderly have slower gastric emptying rates; posture has negligible effect.

Suitable Drugs for Gastro-Retentive Systems

• Drugs with local activity in the stomach (e.g., Misoprostol, antacids).
• Drugs with narrow absorption windows (e.g., L-DOPA, furosemide).
• Instable drugs in intestinal environments (e.g., Captopril, Metronidazole).
• Drugs that affect colonic microbes (e.g., Helicobacter pylori antibiotics).
• Drugs with low solubility at high pH (e.g., Diazepam).

Unsuitable Drugs for Gastro-Retentive Systems

• Drugs with limited acid solubility (e.g., Phenytoin).
• Drugs unstable in gastric environment (e.g., Erythromycin).
• Drugs meant for targeted colonic release (e.g., 5-aminosalicylic acid).

Types of Gastro-Retentive Drug Delivery Systems

• Floating Systems: Low-density systems that remain buoyant in the stomach for prolonged release.
• Expandable Systems: Hydrogels that swell to prevent gastric emptying yet degrade over time.
• Swelling Systems: Superporous hydrogels that expand significantly in gastric fluid.
• Bioadhesive Systems: Adhere to gastric walls, increasing retention time.
• High Density Systems: Designed to sink and remain in the gastric cavity.

Variants of Floating Drug Delivery Systems

• Effervescent Systems: Utilize gas-generating components that create buoyancy.
• Non-Effervescent Systems: Expand through absorption of gastric fluid, preventing exit.
• Colloidal Gel Barrier Systems: Feature rapidly swelling polymers that create a buoyant environment; examples include Madopar and Valrelease.
• Alginate Beads: Floating beads that prolong gastric residence up to 5.5 hours through freeze-dried calcium alginate method.
• Hollow Microspheres/Microballoons: Float in acidic media for over 12 hours utilizing a novel emulsion method.

Requirements for Superporous Hydrogels

• Easily swallowable size, preferably housed in size 000 capsules.
• Fast swelling capability to prevent gastric emptying.
• Swollen size must be large enough to be retained in the stomach.
• Strong enough to withstand gastric contractions and shear forces.

Conclusion

Gastro-retentive drug delivery systems hold promise for improving therapeutic outcomes by enhancing drug retention in the gastric region, targeting specific drugs for effective local action, and tailoring designs to optimize performance based on physiological understanding.

This quiz explores the gastro-retentive drug delivery system, focusing on its objectives, such as prolonging the residence time of oral dosage forms in the stomach. It also highlights its effectiveness in delivering drugs locally for conditions like peptic ulcers. Understanding stomach physiology and function is essential for enhancing patient compliance.