Solid Dosage Forms: Capsules Overview

Solid Dosage Forms: Capsules

• Capsules are solid dosage forms containing medication within a hard or soft gelatin shell.
• Derived from the Latin word "capsula," meaning "small box."

Intended Learning Outcomes

• Students should be able to define capsules as solid dosage forms.
• Students should be able to enumerate the advantages and disadvantages of capsules.
• Students should be able to identify different routes of capsule administration.
• Students should be able to compare filled materials and types of hard gelatin capsules.
• Students should be able to define soft gel capsules as solid dosage forms.
• Students should be able to compare filled materials and types of soft gelatin capsules.

Types of Capsules

• Hard Gelatin Capsules (HGC): Two parts (body and cap).
• Soft Gelatin Capsules (SGC): One piece.

Types of Materials Filled in Capsules

• Dry Solids: Powders, granules, pellets, tablets.
• Semi-solids: Thermo-softening materials, thixotropic materials, pastes.
• Liquids: Water-miscible liquids, water-immiscible oils.
• Granules: Made through granulation; more irregular than pellets, often made through coating or microencapsulation.
• Tablets: Used for special release forms, separating incompatible ingredients, or compounding potent drugs.
• Suspensions: Used for insoluble drugs.
• Water-immiscible oils: Fixed, aromatic vegetable oils, aliphatic, aromatic, chlorinated hydrocarbons, liquid ethers, and esters.
• Water-miscible liquids: PEG 400 and 600, isopropyl alcohol, polyglycerol, triacetin, glyceryl esters, sorbitan esters, sugar esters, polyglyceryl esters, propylene glycol, and glycerol (up to 10% to prevent migration into gelatin and softening).

Limitations of Capsules

• Drugs or excipients with high water or other gelatin solvent concentrations cannot be incorporated.
• Emulsions are not recommended due to instability and cracking during manufacturing.
• Surfactants may negatively affect the capsule shell.
• Extreme pH levels (below 2.5 or above 7.5) should be avoided to prevent gelatin hydrolysis and leakage, or tanning of the gelatin.
• Aldehydes should be avoided as they have a tanning effect on gelatin proteins.

Advantages of Capsules

• Mask the odor and taste of unpleasant drugs.
• Attractive appearance.
• Easy to swallow.
• Require less additives.
• Rapid drug release.
• Offer protection against light.
• Offer protection against air and moisture.
• Gelatin shell is physiologically inert.
• Simplified manufacturing processes on smaller scales.
• Increased flexibility for prescribing dosage and drug combinations.

Disadvantages of Capsules

• Not suitable for liquids that dissolve gelatin.
• Very soluble salts (e.g., bromides, iodides) should not be used to avoid gastric irritation due to localized high drug concentration.

Sizes and Shapes of Capsules

• Capsule sizes range from 000 (largest) to 5 (smallest).
• Size 0 is the largest typically acceptable to patients.

Storage of Capsules

• Store in tightly closed glass containers, protected from dust, humidity, and temperature extremes.
• Capsules generally contain 13-16% moisture.
• High humidity may lead to tackiness due to absorption, while low humidity may result in brittleness.

Preparation of Hard Gelatin Capsules

• Gelatin solution (30-40%): Gelatin and hot demineralized water are mixed under vacuum to remove entrapped air.

Source of Gelatin

• Partial hydrolysis of collagen from animal skin, bones, and connective tissues.
• Contains 18 amino acids, primarily glycine and alanine.
• Two main types: type A (acid hydrolysis of pork skin), type B (alkaline hydrolysis of animal bones).

Gelatin Specifications

• Bloom strength (gel strength): An empirical gel strength measure indicating the gel firmness (150-280g). Higher for soft gelatin.
• Viscosity: Vital to control the cast film thickness (30-60 millipoise).

Other Used Ingredients

• Colorants: Commonly iron oxides to improve patient compliance.
• Opaquing agents: Titanium dioxide to make the shell opaque, often used for protection from light.
• Preservatives: Parabens.

Preparation of the Capsule Shell

• Dipping: Stainless steel pins are dipped into a 50°C heated jacketed dipping pan (dipping time dependent on capsule size).
• Rotation: Spinning the pins distribute gelatin, and cold air can firm the gelatin.
• Drying: Gelatin-coated pins go through a series of drying ovens; dehumidification to prevent film from melting.
• Stripping: Bronze jaws remove the cap and body portions from the pins.
• Trimming: Knives trim the shells to the desired length.
• Joining: Cap and body portions are aligned and pushed together.

Sorting and Printing Capsules

• Sorting: Examining capsules visually and manually removing defects (imperfect cuts, holes, splits, etc.).
• Printing: Empty capsules are printed before filling by rotary presses (up to 3/4 million capsules per hour).

Preparation of Hard Gelatin Capsules:

• Formulation: Selecting the suitable size and adding bulk agents, lubricants, absorbents, or wetting agents.
• Filling: Small-scale (using punch or molds) or large-scale (using automated machines).
• Cleansing and polishing.

Hard Gelatin Capsules Filling:

• Powders: Should be homogeneous, minimize segregation, and have good flow properties for filling each capsule.
  • Drugs: Dose determines the amount of excipients.
  • Excipients: (Diluents) - Lactose, MCC, maize starch, are free-flowing and have plug-forming properties.
• Glidants: Ex. Colloidal anhydrous silica.
• Lubricants: Ex. Magnesium stearate.
• Wetting agents: Sodium lauryl sulphate (1%) to aid poorly soluble drugs solubilization.
• Disintegrants: (Ex. Croscarmellose, cross povidone) - Sometimes included to help disintegration of the gelatin shell. N.B. Starch not used as disintegrant in HGC, as its swelling is insufficient to disrupt the shell).

Small Scale Capsule Filling (Manual):

• Lower halves of capsules are supported in holes of a suppository mold or plastic block.
• Powders are poured into each capsule via a funnel.

Hand Operating Devices (Manually Operated Machines)

• Capsules are placed manually, caps are removed and replaced, and powders are distributed into an empty capsules mechanically using top plate.
  • Powders spread over perforated tray with the powder above the empty body.

Manual Capsule Filling Machine:

• 300 hole operation.

Large Scale Capsule Filling (Semi-automatic and Automated Machines)

• Semi-automatic machines need a human operator to transfer capsules to the next step.
• Automatic machines (e.g., Zanasi, Hofliger, and Karg) are fully automated
  • Features different steps including capsule hopper, rectifying rollers, cap and body segments, powder filling, joining, dispensing, segment cleaning, weight control, control stations, auger motors, auxiliary powder hopper, and more.

Basic Steps (operation) of filling machines:

• Feeding
• Orientation
• Opening
• Ejection of non-separated items
• Dosing
• Closer
• Ejection

Rectification (orientation):

• Putting capsules in a hopper
• Metal fingers strike middle and rectify roller
• Causes capsules to rotate, facing body-end downwards.

Separation of Caps from Bodies:

• Capsules are fed into holders/bushes; body can pass through the upper one but not the caps (transfer typically with vacuum).
• Lower body ring placed on the rotary table, powder hopper moved over it, and auger fills the body.
• After one full turn, hopper returns to original position.

Dosing Fill Material:

• Different methods, one being the auger method used on semi-automatic machines.
• Empty capsules put on ringed holders.
• Bodies passed under a hopper with auger/screw transferring material.

The Dosator:

• Used in fully automatic machines.
• Consists of a dosing tube with a spring-loaded piston.
• Plunger opens the tube into powder bed, creating a plug (slug) of powder.
• Raised/positioned over capsule, and plunger lowered to insert powder.
• Dose adjusted by piston position or powder bed depth.

The Dosing Disk:

• Holes bored through disk; solid brass "stop" plate closes off holes.
• Five sets of pistons in Hofliger-Karg machines compress powder into cavities.
• Cavities indexed, each plug compressed five times per cycle.
• Powder dose controlled by dosing disk thickness (cavity depth), powder bed depth, and tamping pressure.

Replacement of Caps and Ejection of Filled Capsules:

• Cap and body portions rejoined; pins push the filled bodies into the caps.
• Compressed air may be used for pushing the closed capsules out of the bushings.

Locking & Sealing:

• To prevent accidental separation during handling and shipping.

Techniques:

• Park Davis Kapseal: Sealing using a narrow band of colored gelatin.
• Coni-snap: Body rims tapered slightly.
• Coni-snap supro: Caps extend further over the body.
• Capsugel low-temperature thermal: Capsules immersed in hydro-alcoholic solvent then dried with warm air to seal the cap and body.

Soft Gelatin Capsules

• Units with continuous gelatin shell surrounding liquid fill.
• Formed, filled, and sealed in one operation.
• Various shapes and types.
  • Gelatin or other edible polymers & plasticizers.
  • Colorants, opacifiers, and flavors.
  • Possible enteric or delayed-release coating.
  • Water-soluble or oil-soluble fill liquid.
  • APIs in solution or suspensions.
  • Added suspending agents, dispersants, and viscosifiers.

Properties of Capsules

• Hard Gelatin Capsules: Primarily for solids.
• Soft Gelatin Capsules: Suitable for liquids, pastes, drugs susceptible to air deterioration (hermetically sealed). Liquids (except water) acceptable; solids also acceptable.

Shell Wall, Pieces, Shape:

• Hard Gelatin Capsules: Shell wall is thicker. One piece consisting of two pieces (cap and body) sealed, locked, by welding, or mechanical interlocking. Cylindrical shape.
• Soft Gelatin Capsules: Shell wall thinner; One piece. Usually round, oval, oblong, or tubular shapes.

Small and Large Scale Manufacturing:

• Small scale: Can be prepared manually
• Large scale: Often more precisely prepared.

Accuracy in Manufacturing Capsules:

• Small scale: Can be prepared to have less precise measurement.
• Large Scale: Often more accurate.

Operations for shell & filling of capsules:

• Hard Gelatin processes: The shell is made in one operation, and Filling is in a separate operation.
• Soft Gelatin processes: Both the shell and the filling are done in same operation.

Advantages of Soft Gelatin Capsules (SGC):

• Solve compression problems (some drugs unsuitable for tablets).
• Solve mixing and powder flow issues (reducing weight variation and dose discrepancies, especially for potent, low-index drugs).
• Prevent stability issues (e.g., oxidation, hydrolysis, incompatibility from moisture) by encapsulation in a dry shell or using protective environments.
• Aid bioavailability by solubilizing or dispersing drugs in suitable liquid vehicles, optimizing drug dispersion for better absorption.

Storage of Soft Gelatin Capsules (SGC):

• Protect from moisture with containers such as glass bottles with screw caps or waxed seals.
• Maintain temperatures below 30°C for optimal stability.

Evaluation of Capsules (Disintegration Test and Dissolution Test)

• Disintegration Test (BP 1993): Method used to measure the disintegration of tablets or capsules in specified liquid media.
• Dissolution Test (BP 1993): Measures the drug's ability to dissolve in a liquid medium.
• Three types of apparatuses: Basket, Rotating Paddle, and Flow-through cell.

Specifications of the Disintegration and the Dissoltuion Tests:

• Dissolution fluid choices: Depends on the drug substance. (e.g. 0.1M HCl for bases and pH 6.8 phosphate buffer for acidics, and water for neutral drugs/molecules).
• Capsules and tablet compliance: All replicates should complete by standards.
• There should be no significant deviation of individual weight averages than 25% or more

Other Specifications:

• Content uniformity: Ensuring proper mixing by determining the average content of 10 randomly selected capsules. (important for drugs less than 25% weight of total weight or more of total weight).

• Weight Uniformity: Ensuring a consistent dose of drug per capsule for HGCs containing 25% drug or more.

This quiz covers the essential aspects of solid dosage forms, focusing on capsules. Students will learn to define, compare, and discuss the advantages and disadvantages of both hard and soft gelatin capsules. Additionally, it delves into the types of materials that can be filled in capsules and their administration routes.