Pharmaceutical Capsules Quiz

Hard Capsules

• The word "capsule" originates from the Latin word capsula, meaning a small box.
• Two types of capsules exist: hard and soft.
• Hard capsules consist of two cylindrical pieces: a shorter cap that fits over the open end of a longer body.
• Gelatin is the major component of both hard and soft capsules.

Raw Materials

• Gelatin: Non-toxic, readily soluble in biological fluids at body temperature. It forms strong, flexible films from collagen in animal skins and bones. Acid hydrolysis (7-10 days) is often used with porcine skins; bovine bones require a longer basic hydrolysis process. Gelatin quality is assessed by Bloom strength, a measure of gel rigidity (measured in grams required to push a plunger 4mm into gel). Hard capsules use higher Bloom strength gelatin (200-250g) than soft capsules (150g).
• Water: A vital component in gelatin preparations.
• Colorants: Water-soluble dyes or insoluble pigments. Examples include azo dyes, erythrosine (E127), indigo carmine (E132), quinoline yellow (E104), black, red, and yellow iron oxides (E172), and titanium dioxide (E171), which makes the capsule opaque.
• Wetting agents: Surfactants, such as sodium lauryl sulfate, ensure uniform coating of metal molds in the gelatin solution. Essential for smooth operation.
• Preservatives: Added to prevent microbial contamination during manufacture. GMP guidelines limit use of preservatives due to moisture regulation.

Capsule Manufacturing

• Hard Capsule Manufacturing: Metal molds are immersed in a hot gelatin solution. After cooling, the gelatin forms a film. The film is dried, cut to size and removed from the molds. The process is fully automated in specialized facilities.
• Preparation of Raw Materials: Gelatin solutions (35-40% w/v) are prepared in demineralized water at 60-70°C with stirring and vacuum to remove air bubbles. Aliquots are mixed with dye/pigment. Viscosity measurements and adjustments using hot water are crucial in controlling the thickness of the capsule shell. The prepared mixture is transferred to the manufacturing machine.
• Manufacturing Steps: The manufacturing machines consist of two halves, each a mirror image of the other (for cap and body). Molds are made of stainless steel. Capsules are formed by dipping the metal molds into a gelatin solution; the film formed is dried, cut, and the two parts are joined.
• Filling (Powder Formulations): Bench-scale filling uses plastic plates with predrilled holes to hold capsules, with a simple loading device. Capsules are fed into the holes and then the bodies, separating the cap from the body, then filling the bodies with powder, or by using a machine and placing capsules in a tray. Industrial filling machines can vary from semi- to fully automatic, with output rates from 3,000 to 150,000 capsules per hour.
• Two types of dosing systems exist:
  • Dependent Systems: measure powder directly using the capsule body. Only effective if the capsule is filled completely.
  • Independent Systems: independent measuring device for the powder. Capsule may be partially filled. Examples are the dosator system (ejects powder into body using a spring-loaded piston) and the tamping finger and dosing disc system (powder is compressed into a plug using rotating fingers).
• Filling of Pellets: For modified release, pellets are not compressed during filling and may be held by suction in the measuring tube. Pellet size directly affects the fill weight
• Tablet Filling: Tablets can also be added to the capsules, especially when clinical trials require blinded samples. The tablets are often film-coated for protection during transfer.

Capsule Properties

• Empty gelatin capsules contain a significant amount of water. This water acts as a plasticizer for the gelatin film.
• Moisture content ranges from 13% to 16% w/w.
• Gelatin is readily soluble at 37°C; dissolution rate decreases below 26°C. Gelatin becomes insoluble at low temperatures, causing swelling.
• Capsule sizes range from 0 to 4. Filling weight is calculated by multiplying tapped density by the capsule body volume.

Capsule Formulation

• Formulations should be uniformly filled, release active ingredients, and meet the requirements of the Pharmacopoeia.
• Low-dose potent compounds are most easily formulated. High-dose compounds require consideration of excipient concentration to fit the capsule size.
• Powder formulations need good flow, minimal or no adhesion between particles, and adequate cohesive properties for plug formation.

Drug Release

• The first stage is capsule disintegration.
• Formulation factors like drug particle size, diluent solubility, lubricant level, surfactants, and disintegrants affect drug release.
• Excess lubricant improves filling but may inhibit release.
• Optimization of formulation parameters, using statistical tools, helps ensure consistent product quality.

Modified Release

• Floating (gastro-retentive) Capsules: Contain hydrophilic polymers (e.g., methylcellulose) to swell in water and create buoyancy. This prolongs gastric retention time and maintains a continuous drug flow to the intestines.
• Gastro-resistant Capsules: Contain enteric coatings that protect acid-sensitive drugs from degradation before reaching the lower gut.

Capsules for inhalation

• Micronized drugs, with low fill weights (less than 25 mg) are filled into capsules.