Gelatin Capsules and Manufacturing Processes

Capsules

• Capsules are a small box, the second most popular oral dosage form.
• Capsule administration can involve swallowing whole or opening and sprinkling contents on food.
• Capsules have advantages over tablets, including elegance, ease of swallowing, and the ability to mask odors and tastes.
• Capsules can be made opaque, which is beneficial for photosensitive drugs.

Types of Capsules

• Hard gelatin capsules consist of two pieces (cap and body) that fit together. They are manufactured and filled separately.
• Soft gelatin capsules are manufactured and filled in a single operation.

Raw Materials for Gelatin Capsules

• Raw materials for hard and soft capsules are similar.
• Gelatin is the main component, a good film-forming material.
• Gelatin undergoes a reversible phase change from solution to gel at temperatures close to ambient.
• It's readily soluble in biological fluids at body temperature and non-toxic.
• Animal bones and skins are the raw materials for gelatin, prepared through collagen hydrolysis.
• Two types of gelatin exist: Type A (acid hydrolysis) and Type B (basic hydrolysis).

Plasticizers

• Hard gelatin capsules have less plasticizer than soft gelatin capsules.
• Common plasticizers include glycerol, sorbitol, propylene glycol, sucrose, and acacia.

Colorants

• Soluble dyes (mainly synthetic) or insoluble pigments (like titanium dioxide and iron oxides) can be used as colorants.
• There's a trend towards using insoluble pigments, particularly iron oxides, instead of soluble dyes.

Preservatives

• Preservatives are sometimes added to prevent microbiological contamination during manufacturing.

Hard Gelatin Capsules (Details)

• Available in sizes 000 to 5 (000 is largest, 5 is smallest).
• Capacity varies according to the density and compressibility of the powder filling.
• Used for powder, granules, tablets, pellets, beads, semi-solids, and thermo-softening materials.

Basic Requirements for Capsule Fillings

• Dosage needs to be accurate.
• Active ingredients should release in a usable form to the patient.
• The filling should not react with gelatin (e.g., avoid aldehydes).
• The filling shouldn't interfere with the capsule shell (e.g., water softening).
• Incompatible ingredients within the same capsule can be separated by coating one ingredient or placing the substances in separate small capsules inside a larger one.

Locking and Sealing of Capsules

• Techniques include using a narrow band of gelatin, spot welding with a hot probe, segmented raised collars, and moistening the caps' inner surface with water.

Filling of Hard Gelatin Capsules

• Filling can be hand-operated or involve various forms of semi-automatic or fully-automatic machines that handle removal, filling, replacement and ejection of filled capsules.

Soft Gelatin Capsules (Differences)

• Soft gelatin capsules can hold solids, liquids, and semi-solids.
• Gelatin, colorants, and plasticizers can be used.
• Soft gelatin capsules are more flexible than hard ones.
• Soft gelatin capsules are filled and sealed in a single step.

Composition of Soft Gelatin Capsules

• Sugar is replaced with plasticizers to impart elasticity.
• These can contain up to 5% sugar, mainly for chewable properties.
• Formulations include spheres (pearls) and globules with capacities ranging from 1 to 480 minims.
• The filling materials include combinations of liquids, solutions, suspensions, semi-solids, or dry powders; only substances that don't dissolve gelatin should be used (like oils).

Manufacture Methods

• Plate method (small scale): involves placing gelatin sheet over a die plate with pockets, drawing the sheet into the pockets with vacuum, filling the pockets, placing another sheet on top, and using machine pressure to form and cut out the capsules.
• Rotary die process (Scherer): uses rotary drums to spread gelatin solution into sheets, which are fed between rotary dies. This process heats the gelatin and seals/cuts the capsules from the sheets in a continuous operation.

Seamless Gelatin Capsules

• Not sealed by pressure from two gelatin sheets.
• Cold liquid paraffin (4°C) is used because it's non-solvent and solidifies gelatin.

Sustained Released Capsules

• More efficient drug utilization.
• Reduced total drug intake.
• More convenient administration.
• Dosage forms have immediate- and sustained-release portions, controlling drug release rate equal to its elimination/detox rate.
• Suitable uses include chronic conditions, but not for rapidly-acting antibiotics or muscle relaxants.

Sustained Released Dosage Forms

• Hard gelatin capsules, medicated and pan-coated onto sugar starch beads, releasing medication initially.
• Remaining beads are coated with fatty/waxy substances (beeswax, glyceryl monostearate, ethyl cellulose).
• Drug release depends on moisture penetration into the fatty/waxy coat.
• Sustained release portions are coated with styrene-maleic acid copolymers.
• Drug release is based on pH sensitivity (disintegrating at intestinal pH) and stomach emptying rate.
• Cationic drugs can be absorbed onto cationic exchange resins, affecting release rates.

Enteric Coated Capsules

• Capsules resist gastric dissolution, releasing contents in the intestine for uses like when a drug is inactive/irritating in stomach or needs high intestinal concentration.
• Coating materials include shellac, cellulose acetate phthalate, fatty/waxy materials and formaldehyde treatment to harden gelatin and form methylene bridges.
• Coating is done by a method that uses cellulose acetate phthalate solution to coat capsules for a minute and drying on gauze.

Dissolution Rate of Drugs from Capsules

• Affected by shell dissolution rate, the medium penetration rate into the powder, rate of powder aggregation, and the primary particle's nature.
• Dissolution is the rate-determining step in absorption influencing the drug's availability for absorption in the gastrointestinal fluid.

Formulation Factors Affecting Drug Availability

• Active ingredients: physicochemical properties (solubility, melting point, crystalline form) affect solution rate proportionally to surface area. Smaller particles have larger surface areas.
• Additives:
• Diluents: inert materials increasing mixture volume, choice based on active ingredient's solubility and proportion. Common diluents include lactose, dicalcium phosphate, and microcrystalline cellulose.
• Disintegrants: help break up the powder efficiently without affecting solubility of active ingredients (starch grains).
• Lubricants/Glidants: improve filling properties and sometimes affect drug release. Magnesium stearate is a common example.
• Surfactants/Wetting agents: increase powder wettability, commonly used to overcome the hydrophobic effect of magnesium stearate.

Factors Affecting Bioavailability in Soft Gelatin Capsules

• Solubility: Acid-soluble drugs dissolve quickly in the stomach, leading to quicker distribution.
• Particle size: Smaller particles have higher surface areas and faster dissolution rates.
• Vehicle: hydrophilic (water-loving) or hydrophobic (water-fearing) vehicles are used based on the drug's nature.
• Suspending agents: Increase bioavailability of insoluble drugs.

Evaluation of Commercial Capsules

• Weight variation method involves weighing 10 capsules, removing contents, and reweighing each part and the whole to calculate the net weight of the contents and the degree of accuracy in the content of each dose.
• Content uniformity ensures consistent drug amounts per capsule in a batch.
• It calculates whether a batch of capsules is of the correct strength.
• Dissolution test measures how quickly a drug is released from the capsule shell in a specified medium.

Moisture Permeation Test

• The test is used to determine how much water or moisture permeates the packaging a dosage unit
• Assess moisture absorption over time.

Test your knowledge of gelatin capsules and their manufacturing processes with this quiz. Explore topics such as the advantages of capsules over tablets, materials used in capsule production, and techniques for ensuring capsule quality. Perfect for students and professionals in pharmaceutical sciences.