Capsule Dosage Forms Overview

Capsules

• Hard gelatin capsules are capsules with a rigid shell made from gelatin
• Soft gelatin capsules are capsules with a pliable and less rigid shell made from gelatin
• Capsules can be used for oral, rectal and vaginal administration
• Capsules are convenient for patients as they mask the taste and smell of the active drug

Advantages of Capsule Dosage Form

• Easy to prepare
• Can vary dosage and drug combination

Disadvantages of Capsule Dosage Form

• Not suitable for administering very soluble ionic salts (e.g., potassium chloride, ammonium chloride)

Hard Gelatin Capsules

• The capsules are manufactured by creating a shell out of a gelatin solution

Steps Involved in Hard Gelatin Capsule Preparation

• Comminution: The process of reducing particle size of the drug to a uniform size
• Blending: The process of combining and ensuring uniform distribution of the active ingredients throughout the formulated mixture
• Determine capsule size: Ensure the correct size of the capsule is selected based on the drug or drugs being formulated
• Encapsulate: Filling the capsule shells with the formulated drug mixture by hand or using a capsule filling machine
• Clean: Capsules are cleaned to remove excess powder or debris adhering to the shell
• Quality control: Ensuring the final product meets the required specifications

Capsule Sizes for Human Use

• 000
• 00
• 0
• 1
• 2
• 3
• 4
• 5

Capsule Sizes for Veterinary Use

• 7
• 10
• 11
• 12
• 13

Rules for Capsule Sizes

• Rule of 6's: a rule to approximate the weight of powder that will fit in a specific capsule size
• Rule of 7's: a rule to approximate the weight of powder that will fit in a specific capsule size

Important Considerations when Developing the Formulation and Choosing Capsule Size

• Accurate Dosage: Ensure the final capsule dosage is correct and represents the desired amount of the drug
• Bioavailability: The capsule's formulation must allow for good and consistent absorption of the drug by the body
• Ease of filling and Manufacturing: The formulation must be easy to fill into the capsule shells, both on a small scale and for large-scale manufacturing
• Stability: The formulation should be stable over time, meaning it should not deteriorate or change significantly in terms of its composition or effectiveness.
• Elegance: The final product should have a pleasing and appealing appearance

Considerations for Capsule Formulation

• Incompatibilities: Checking for any potential incompatibilities between drug ingredients
• Hygroscopic: Determines if the raw materials are hygroscopic, meaning they attract and absorb moisture from the air
• Deliquescent: Determine if the raw materials are deliquescent, meaning they absorb moisture from the air to the point they dissolve
• Eutectic: Checking for eutectic mixtures, where two ingredients in a mixture lower the melting point of each other
• Diluents and Adsorbents: Determining the need to use diluents and adsorbents to adjust the bulk volume and flow characteristics of the final formulation
• Special Applications: Special considerations for potent powders, tablets within capsules, capsules within capsules, and altered-release capsule formulations.

Methods for Filling Hard Capsule Shells

• Punch method
• Capsule filling machines
• Automated filling machines

Capsule Sealing Techniques

• Kapseals
• Gelatin bands

Methods for Cleaning Capsules

• Cleaning Vacuum

Soft Gelatin Capsules

• Soft gelatin capsules are made by manufacturing a film-like shell of gelatin and filling with the final formulation
• Soft gelatin capsules can contain water immiscible volatile liquids, nonvolatile liquids, water-miscible nonvolatile liquids and water-miscible nonvolatile compounds

Steps Involved in Soft Gelatin Capsule Preparation

• Plate process
• Molds
• Rotary die process

Capsule Quality Control

• This ensures the quality and safety of the final product
  • Drug Content: Analyzing the amount of active drug inside the capsule
  • Fill Weight: Measuring the weight of the contents in each capsule
  • Disintegration: Testing the capsule's ability to break down in the appropriate time frame
  • Dissolution: Assessing the rate and amount of active drug dissolving from the capsule
  • Stability: Evaluating the capsule's shelf life and how it maintains its potency and quality over time

Important Compendial Requirements

• Containers for Dispensing Capsules: Requirements for the type of container used to package capsules and how they protect the contents from environmental factors
  • Tight
  • Well-closed
  • Light resistant

Disintegration Testing

• Ensures the capsule breaks down into a soft mass and no undissolved core is present remaining.

Dissolution Testing

• This test assesses how well the drug dissolves from the capsule to ensure its bioavailability
• To ensure the capsule meets quality control requirements.

Weight Variation

• This test measures the weight of the contents in each capsule.
• The test is required for hard and soft gelatin capsules.

Content Uniformity

• This test determines the range of active drug variation in each capsule.
• The test is required for hard and soft gelatin capsules.

Content Labeling Requirement

• Required for all official capsules
• The quantity of each active ingredient in each dosage unit must be expressed on the container label

Stability Testing

• The capsule's stability testing ensures the product’s effectiveness and safety over time
• Factors that affect stability include temperature, humidity, light, formulation components, the container and closure system.

Moisture Permeation Test

• This test is used to measure the amount of moisture that can penetrate single- and unit-dose containers.

Packaging and Storage

• Capsules are generally stored at room temperature,
• Specific storage conditions may be required depending on the active drug.

Patient Counseling for Capsules

• Provide information about swallowing capsules
• If the capsule is larger than size #5, recommend methods to help patients take the capsule such as using syrup, honey, or liquid candy
• Instruct patients to be cautious when emptying the contents of capsules into food, etc.
• Inform patients about the different routes of administration (oral, rectal, vaginal).

Administration of Capsules

• Swallow capsule with liquid
• Dissolve contents in water or mix contents with food

Example Formulations

• Morphine Sulfate 10-mg and Dextromethorphan HBr 30-mg Capsules
• Progesterone 100 mg in Peanut Oil Capsules
• Triple Estrogen Capsules, Semisolid Fill