Introduction to Capsules & Pellets
Capsules are the second most popular solid dosage form after tablets. They offer elegant appearance, easy swallowing, and the ability to mask unpleasant tastes completely. This unit covers the industrial manufacturing of Hard Gelatin Capsules (two-piece shells filled with powders, granules, or pellets) and Soft Gelatin Capsules (one-piece sealed shells containing liquids or semi-solids). It also introduces Pelletization — the process of creating uniform spherical drug pellets for modified-release formulations.
Syllabus & Topics
- 1Introduction to Capsules: Solid dosage forms where drug is enclosed in a hard or soft soluble shell (usually gelatin). Advantages: mask bitter taste/odor completely, easier to swallow than tablets, elegant appearance, rapid disintegration (faster drug release than tablets), suitable for liquid fills.
- 2Gelatin: Protein derived from controlled hydrolysis of collagen from animal bones (Type B – alkali-treated, higher bloom strength) and skin (Type A – acid-treated). Bloom strength (gel rigidity) determines shell quality. Cross-linking of gelatin by aldehydes (formaldehyde from Rayon in packaging) reduces dissolution → pellicle formation.
- 3Hard Gelatin Capsules – Shell Production: Dip-coating process. Stainless steel pins dipped into hot gelatin solution (30-40% w/w) → withdrawn → dried in kilns → trimmed to size → joined as cap-body pairs. Shell composition: Gelatin + Water (13-16%) + Opacifier (TiO₂) + Colorants + Preservative.
- 4Hard Capsule Sizes: Sizes range from 000 (largest, ~1.37 mL) to 5 (smallest, ~0.13 mL). Size 0 is most commonly used. Human use: 000 to 5. Veterinary: even larger sizes available. Selection depends on bulk density of fill material and required drug dose.
- 5Hard Capsule Filling Methods: (1) Manual/Bench-top (small scale). (2) Semi-automatic (Zanasi, Osaka machines). (3) Fully automatic (Bosch GKF, MG2 – dosator or dosing disc principle). Steps: Rectification (orientation) → Separation of cap from body → Filling (auger, tamping, dosator) → Rejoining → Ejection.
- 6Finishing & Special Techniques: Banding (gelatin band around cap-body seal for tamper evidence), Sealing (heat or solvent welding), Polishing (in rotating pans with wax). Special fills: pellets, mini-tablets, semi-solids, liquid fills in hard capsules (using LEMS technology – Liquid Encapsulation Micro-Spray).
- 7Hard Capsule Manufacturing Defects: Splits/cracks in shell (low moisture <12%), Telescoping (body pushed into cap), Dented/punctured shells (mechanical damage), Non-uniform fill weight (poor powder flow), Empty capsules (filling mechanism failure).
- 8Hard Capsule QC Tests – In Process: Lock length, shell moisture (13-16%), weight variation of empty shells. Final Product: Weight variation (IP: ±10% for <300mg), Content uniformity (85-115%), Disintegration test (IP: <30 min in water at 37°C), Dissolution test, Microbiological limits.
- 9Soft Gelatin Capsules – Shell Composition: Gelatin + Plasticizer (Glycerin or Sorbitol, 20-30% of wet gel – determines flexibility) + Water. Ratio of plasticizer:gelatin (Dry) determines whether shell is soft or hard. Opaquant-extenders (TiO₂) for light protection.
- 10Soft Capsule Content: Must be liquid or semi-solid. Oily liquids, non-aqueous solutions, suspensions in oil, self-emulsifying drug delivery systems (SEDDS). Water and low-pH solutions CANNOT be filled (dissolve gelatin shell). PEG 400 fills are possible.
- 11Base Adsorption & Minim/Gram Factor: Base adsorption defines the capacity of a given liquid base to absorb a specific amount of solid drug powder while remaining fluid enough to fill. Minim/gram factor converts between weight and volume for accurate fill calculations.
- 12Soft Capsule Production – Rotary Die Process (Scherer): Continuous process. Two ribbons of warm gelatin film pass between counter-rotating dies that simultaneously form, fill (via injection wedge), and seal capsules in one step. Production rate: 25,000-30,000 capsules/hour. Most widely used commercial process.
- 13Soft Capsule QC, Packing & Stability: QC: Weight variation, content uniformity, disintegration (<30 min), dissolution, leakage test, seal integrity. Storage: 20-25°C, 40-60% RH (too dry → brittle shells, too moist → soft/sticky shells). Photosensitive fills require opaque shells.
Learning Objectives
Frequently Asked Questions (FAQs)
Q1. What Is the Difference Between Hard and Soft Gelatin Capsules?
Hard gelatin capsules consist of two rigid pieces (a cap and a body) that are filled with powders, granules, or pellets. Soft gelatin capsules are one-piece, hermetically sealed flexible shells that contain liquids, oils, or semi-solid formulations and are plasticized with agents such as glycerin or sorbitol. Hard capsules are manufactured first and then filled in a separate step, whereas soft capsules are formed, filled, and sealed simultaneously using the Rotary Die Process.
Q2. Why Can’t Water-Based Solutions Be Filled into Soft Gelatin Capsules?
Soft gelatin capsules typically contain about 30–40% water in their shell. If water-based liquids are used as fills, an osmotic gradient develops that causes water to migrate between the shell and the fill, potentially dissolving or weakening the capsule shell. Therefore, non-aqueous liquids such as oils or polyethylene glycol solutions are used, and the fill formulation must maintain a pH between about 2.5 and 7.5 to prevent gelatin degradation.
Q3. What Is Extrusion–Spheronization?
Extrusion–spheronization is a widely used pelletization method for producing spherical pellets. The process begins with wet granulation of drug and excipients (commonly Microcrystalline cellulose) with water. The wet mass is extruded through a screen to form cylindrical rods (extrudates). These rods are then placed in a spheronizer, where a rapidly rotating friction plate rounds them into uniform spherical pellets, followed by drying. Microcrystalline cellulose is critical because it retains water and provides plasticity necessary for sphere formation.
Q4. What Is the Pellicle Problem in Capsule Dissolution?
Pellicle formation occurs when gelatin undergoes cross-linking reactions, creating an insoluble membrane around the capsule that prevents normal dissolution. This can result from exposure to aldehydes (such as formaldehyde from packaging materials), high temperature and humidity during storage, or reactive fill ingredients. To overcome this issue during dissolution testing, enzymes such as pepsin or pancreatin are sometimes added to the dissolution medium to break down the pellicle.
Q5. What Are Non-pareil Beads Used for in Pelletization?
Non-pareil beads, also known as sugar spheres, are inert spherical cores used as starter seeds in the drug layering technique. A drug solution or suspension is sprayed onto these rotating beads using equipment such as a Wurster fluidized bed coater. Successive layers form uniform drug-coated pellets, which can later be coated with polymers to achieve modified-release formulations.