Precautions and Process Requirements for Gelatin in Hard and Soft Capsules

As the core film-forming material of hard and soft capsules, gelatin requires strict quality and process control to ensure capsule stability and drug safety.

Precautions for Use

1. Purity Control: Select pharmaceutical-grade gelatin to avoid excessive heavy metals (e.g., lead, mercury) and microorganisms, preventing capsule deterioration or safety risks.
2. Humidity Management: Gelatin is highly hygroscopic. The storage environment humidity should be maintained at 45%-65% to avoid capsule softening, adhesion, brittleness, or cracking. Workshop humidity during production also needs control to ensure molding quality.
3. Compatibility with Contents: Conduct compatibility tests in advance. Strong acids, alkalis, or oxidizing components in the contents may damage gelatin structure.

Process Requirements

• Hard Capsules: Precisely control gelatin solution concentration (typically 12%-15%) and temperature (50-60℃) to ensure uniformity without bubbles, maintaining a consistent capsule shell thickness (generally 0.15-0.25mm). Dry for 24-48 hours post-molding, with final moisture content stabilized at 12%-16%.
• Soft Capsules: Add plasticizers (e.g., glycerol) to gelatin solution at a ratio of gelatin:glycerol = 1:0.3-0.5 to enhance flexibility. Control pelleting temperature at 20-30℃ to prevent deformation. Dry for 48-72 hours, with moisture content maintained at 12%-16% for storage stability.

Significant differences exist in gelatin type, specification, and quality requirements between soft and hard capsules, stemming from their distinct manufacturing processes and physical form needs.

1. Differences in Gelatin Type

While chemically identical, gelatin’s physical properties—determined by raw material sources and processing—make it suitable for different capsule types.

• Hard Capsules: Prioritize "hardness" and "stability". Bone gelatin is widely used for its higher gel strength.
• Soft Capsules: Prioritize "elasticity" and "film-forming ability". Skin gelatin (e.g., bovine hide, pork skin gelatin) meets manufacturing needs with suitable viscosity and plasticity, reducing deformation or cracking.

1. Differences in Gelatin Specifications

Key parameters (gel strength, viscosity, moisture) directly affect process adaptability:

1. Gelatin for Hard Capsules

• Gel Strength: Core indicator, requiring ≥220 Bloom g. Higher gel strength ensures better hardness and impact resistance, preventing breakage.
• Viscosity: Controlled at 25-40 mPa・s (at 60℃). Moderate viscosity avoids thin, brittle shells (too low) or reduced molding efficiency (too high).
• Moisture: ≤12%. Excess moisture causes softening/adhesion; insufficient moisture leads to brittleness.

2. Gelatin for Soft Capsules

• Gel Strength: Lower requirement, typically ≥180 Bloom g. High hardness is unnecessary; elasticity is prioritized—excess gel strength results in rigid, brittle shells.
• Viscosity: Higher requirement, 40-60 mPa・s (at 60℃). High viscosity ensures uniform film formation and shape retention post-molding.
• Moisture: ≤13%. Slightly higher than hard capsules to maintain elasticity and prevent dry cracking.

1. Common Quality Requirements (Pharmacopoeial Standards)

Both capsule types require pharmaceutical-grade gelatin meeting the following safety and applicability criteria:

1. Purity: Free of excessive heavy metals (e.g., lead ≤0.1 mg/kg, arsenic ≤0.05 mg/kg), microorganisms (complying with sterility/microbial limit standards, e.g., no Escherichia coli detected), and harmful impurities.
2. Transparency & Color: Colorless or pale yellow, without obvious turbidity or foreign matter, ensuring clean, uniform appearance.
3. pH Value: 5.5-7.5 (near neutral) to avoid acid-base reactions with contents, protecting drug stability.
4. Ash Content: ≤2.0%, reflecting purity—excess ash indicates inorganic impurity contamination.
5. Solubility: Swells and dissolves slowly in water, disintegrates rapidly in gastric fluid to ensure content release efficiency.