Detailed Explanation of Hard Capsules PDF

Detailed Explanation of Hard Capsules 1. Introduction to Hard Capsules - Capsules are containers for active pharmaceutical ingredients (APIs), designed to be easily swallowed. - Hard capsules consist of: - Cap: A shorter, cylindrical piece that fits over the body. - Body: A longer piece that...

Detailed Explanation of Hard Capsules 1. Introduction to Hard Capsules - Capsules are containers for active pharmaceutical ingredients (APIs), designed to be easily swallowed. - Hard capsules consist of: - Cap: A shorter, cylindrical piece that fits over the body. - Body: A longer piece that holds the medication. - Their primary component is gelatin, derived from animal sources, making them flexible and strong. 2. Raw Materials Used in Hard Capsules a. Gelatin - Preparation: - Derived by hydrolysis of collagen from animal skins and bones. - Two processes: - Type A: Acid hydrolysis (faster process, primarily for porcine skin). - Type B: Basic hydrolysis (slower process, used for bovine bones). - Important Properties: - Bloom Strength: Measures gel rigidity. Hard capsules need higher bloom strength (200-250 g) than soft capsules. - Viscosity: Affects shell thickness and consistency. b. Colorants - Types: - Water-soluble dyes: Synthetic, including azo dyes (with -N=N- linkage) and non-azo dyes. - Insoluble pigments: Titanium dioxide (white), iron oxides (red, yellow, black). - Used to make capsules opaque or colored. c. Wetting Agents - Example: Sodium lauryl sulfate. - Role: Ensures metal molds are uniformly coated during dipping. d. Preservatives - Used to prevent microbial contamination. - Modern manufacturing, adhering to GMP (Good Manufacturing Practice), regulates moisture content (13-16%) to reduce microbial growth, eliminating the need for preservatives. 3. Manufacturing of Hard Capsules Overview - Involves dipping metal molds into a hot gelatin solution. - The gelatin forms a film on the mold, which is dried and cut to size. - The process is now fully automated for efficiency and consistency. Detailed Steps 1. Preparation of Gelatin Solution: - Gelatin (35-40% w/v) is dissolved in demineralized water at 60-70 °C. - Dyes/pigments are added, and viscosity is adjusted to control shell thickness. 2. Dipping and Drying: - Metal molds ("pins") are dipped into the gelatin solution.  - A gelatin film forms on the molds, which are then air-dried. 3. Cutting and Assembly: - Films are cut into caps and bodies. - The two parts are assembled in a "prelocked" position to avoid separation before filling. 4. Sorting and Quality Control: - Defective capsules are removed mechanically or electronically. - Modern capsules have self-locking features to prevent spillage. 4. Properties of Empty Capsules - Moisture Content: - Capsules contain 13-16% water, acting as a plasticizer. - Loss of moisture makes them brittle; excess moisture softens them. - Solubility: - Readily dissolves at 37 °C (body temperature). - Below 26 °C, capsules absorb water and swell instead of dissolving. 5. Capsule Sizes - Standard sizes for human use 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. 6. Capsule Filling Materials Suitable for Filling 1. Dry Solids: Powders, granules, pellets, tablets. 2. Semi-Solids: Thermo-softening mixtures, pastes. 3. Liquids: Only non-aqueous liquids are used due to gelatin sensitivity to water. Filling Methods 1. Bench-Scale: - Manual devices (e.g., "Feton" device) fill capsules by spreading powder over locked capsule bodies. 2. Industrial-Scale: - Machines fill 3,000-150,000 capsules per hour. - Two dosing systems: - Dependent: Powder is directly measured by the capsule body. - Independent: Powder is pre-measured as a plug before being transferred to the capsule body. 7. Drug Release from Capsules - The capsule shell disintegrates in liquid, releasing the contents. - Key Factors Influencing Drug Release: - Particle Size: - Smaller particles dissolve faster due to increased surface area. - However, very small particles may aggregate, reducing effective surface area. - Diluent Solubility: - Soluble diluents enhance drug release. - Lubricants: - Excess levels reduce wettability and slow drug release. - Surfactants and Disintegrants:  - Surfactants like sodium lauryl sulfate improve dissolution. - Superdisintegrants, which swell significantly, are more effective than traditional starch disintegrants. 8. Modified-Release Capsules 1. Floating (Gastro-Retentive): - Contain polymers like methyl cellulose that swell in water and float in the stomach, prolonging drug release. 2. Gastro-Resistant: - Designed for acid-sensitive drugs or distal intestine delivery. - Achieved through enteric coating on the shell or enteric-coated pellets. 9. Specialized Capsules - Inhalation Capsules: - Contain micronized APIs for inhalation devices. - Fill weight is low (