Pharmaceutical Science: Hard Capsules Overview

Hard Capsules: Detailed Explanation

• Capsules are containers for active pharmaceutical ingredients (APIs), designed for easy swallowing.
• Hard capsules consist of a cap (shorter, cylindrical) and a body (longer, holds medication).
• The main component is gelatin, derived from animal sources (skins and bones), making them strong and flexible.

Raw Materials in Hard Capsules

Gelatin

• Prepared by hydrolyzing collagen from animal skins and bones via two processes:
  • Type A: Acid hydrolysis (faster, primarily for porcine skin).
  • Type B: Basic hydrolysis (slower, used for bovine bones).
• Important properties include:
  • Bloom strength: Measures gel rigidity (higher is better; 200-250g for hard capsules, more than soft capsules).
  • Viscosity: Affects shell thickness and consistency.

Colorants

• Types include water-soluble dyes (synthetic, azo dyes with -N=N- linkage) and insoluble pigments (TiO2, iron oxides).
• Used to make capsules opaque or colored.

Wetting Agents

• Example: sodium lauryl sulfate.
• Ensures uniform coating of metal molds during dipping.

Preservatives

• Used to prevent microbial contamination. Modern manufacturing (with GMP adherence) regulates moisture content (13-16%) to minimize the need for preservatives.

Hard Capsule Manufacturing

• The process involves dipping metal molds into a hot gelatin solution, forming a film that dries and is cut to size.
• The process is fully automated for efficiency and consistency.

Detailed Steps in Manufacturing

1. Gelatin solution preparation: Gelatin (35-40% w/v) dissolved in demineralized water (60-70°C). Dyes/pigments added, and viscosity adjusted for shell thickness control.
2. Dipping and drying: Metal molds are dipped into the gelatin solution, and the solution is dried to form capsules.

Capsule Assembly & Quality Control

• Films are cut into caps and bodies, then assembled in a "prelocked" position to prevent separation.
• Defective capsules are removed mechanically or electronically. Modern capsules have self-locking features preventing spillage.

Properties of Empty Capsules

• Moisture Content: 13-16%, acting as a plasticizer. Loss of moisture makes them brittle, and excess moisture softens them.
• Solubility: Dissolves readily at 37°C (body temperature). Below 26°C, they absorb water and swell instead of dissolving.

Capsule Sizes

• Standard sizes range from size 0 (largest) to size 4 (smallest).

Volume Estimation

• For powders: Multiply capsule body volume by powder density.
• For liquids: Multiply liquid specific gravity by capsule volume, then adjust by 0.9.

Capsule Filling Materials

• Dry solids: Powders, granules, pellets, and tablets.
• Semi-solids: Thermo-softening mixtures, pastes.
• Liquids: Only non-aqueous liquids due to gelatin's sensitivity to water.

Filling Methods

• Bench-Scale: Manual devices (e.g., "Feton" device) spread powder over locked capsule bodies.
• Industrial-Scale: Machines fill 3,000-150,000 capsules per hour, using two dosing systems (dependent and independent).

Drug Release from Capsules

• Capsule shell disintegration in a liquid releases the contents.
• Key factors influencing drug release:
  • Particle size (smaller dissolves faster).
  • Diluent solubility (soluble diluents enhance release).
  • Lubricants (excess levels slow drug release).
  • Surfactants and disintegrants (improve dissolution).

Modified-Release Capsules

1. Floating (Gastro-Retentive): Contain polymers (methyl cellulose) that swell and float in the stomach, prolonging drug release.
2. Gastro-Resistant: Designed for acid-sensitive drugs or distal intestine delivery achieved via enteric coating.

Specialized Capsules

• Inhalation Capsules: Contain micronized APIs for inhalation devices. Fill weight is typically less than 25mg, requiring precise filling machines,.

Formulation Optimization

• Formulation must ensure:
  • Uniform filling and stability.
  • Effective release and absorption of API.
  • Compliance with pharmacopoeial standards.
• Factors like lubricant concentration, particle size, and excipient selection are optimized using statistical tools.