Dissolution Test For Solid Dosage Form: Learn in 7 Minutes

The Dissolution test is an important quality control (QC) procedure used in the pharmaceutical industry to evaluate the release rate of the active pharmaceutical ingredient (API) from solid oral dosage forms, such as tablets and capsules, into a dissolution medium under controlled conditions. This test helps assess the bioavailability of the drug, ensuring that it will dissolve in the gastrointestinal tract as intended to exert its therapeutic effect.

Dissolution Test For Solid Dosage Form

Drug dissolution testing provides important in vitro drug release information for both quality control purposes (e.g., to assess batch-to-batch stability of solid oral dosage forms such as tablets or capsules) and drug development (e.g., to predict in vivo drug absorption).

Purpose

The dissolution testing provided the following information:

1. Evaluate drug release rate: It measures the amount of drug released from the dosage form over time.
2. Ensure batch consistency: It ensures the consistency and uniformity of drug release between different production batches.
3. Regulatory requirement: Regulatory agencies like the FDA and EMA require dissolution testing to approve new drug products.
4. Help in formulation development: It assists in the development of formulations and selecting the right excipients.
5. Predict bioavailability: Dissolution testing can predict the bioavailability of a drug, which is its availability for absorption after ingestion.

Components Of the Dissolution Test

The following are the key components of the dissolution test:

1. Apparatus: The most common apparatus used are:
   • Apparatus 1 (Basket Method): A basket made of wire mesh that holds the dosage form. It is rotated in a liquid medium.Apparatus 2 (Paddle Method): A paddle that stirs the liquid medium while the dosage form is submerged.
   Both apparatus types are designed to simulate conditions in the gastrointestinal tract.
2. Medium: The medium mimics the pH and composition of the stomach and intestine. Common media include:
   • Water
   • Phosphate buffer solutions
   • Simulated gastric fluid (SGF)
   • Simulated intestinal fluid (SIF) The selection of the dissolution medium is important for ensuring the test conditions are representative of the drug’s behavior in the body.
3. Temperature: The temperature is typically set at 37°C (±0.5°C), which is the standard body temperature, to simulate physiological conditions.
4. Time Intervals: The dissolution process is monitored at different time points (e.g., 5, 10, 15, 30, 60 minutes) to determine how much drug has been released over time.
5. Sampling: At each time point, a sample of the dissolution medium is withdrawn and analyzed for the concentration of the drug, usually through high-performance liquid chromatography (HPLC) or UV spectroscopy.

Dissolution Test Procedure

1. Preparation of the Dissolution Apparatus: Fill the dissolution vessel with the chosen dissolution medium, maintaining the temperature at 37°C.
2. Inserting the Dosage Form: The dosage form (tablet or capsule) is placed in the basket or under the paddle.
3. Starting the Test: The dissolution apparatus is set to the appropriate speed (usually 50-75 rpm for the paddle method).
4. Sampling: At predefined time points, a sample is withdrawn from the dissolution medium and replaced with fresh medium to maintain constant volume.
5. Analysis: The drug concentration is determined using a suitable analytical technique like UV spectrophotometry or HPLC.

Results and Interpretation

• Dissolution Profile: The amount of drug dissolved over time is plotted to create a dissolution profile. This helps determine if the drug release is within the acceptable range defined by regulatory standards.
• Comparison to Specifications: The results are compared to predetermined specifications or pharmacopoeial standards (such as USP, BP, or EP) for the dissolution of the specific dosage form.
• Release Criteria: Typically, dissolution is considered acceptable if 80% or more of the drug is released within a specified time (e.g., 30 minutes or 60 minutes), but this can vary depending on the drug and dosage form.

Factors That Influence Dissolution Test

The Dissolution Test is influenced by several factors such as:

• Formulation: The type of excipients (binders, fillers, disintegrants, etc.) and the drug’s solubility characteristics.
• Dosage form design: Whether the dosage form is immediate-release, controlled-release, or extended-release.
• pH of the medium: The solubility of some drugs is pH-dependent, and the choice of dissolution medium must account for this.
• Temperature and agitation: The rate of dissolution can be influenced by changes in temperature or stirring speed.

Dissolution Acceptance criteria

The acceptance criteria for the dissolution test of solid oral dosage forms (e.g., tablets and capsules) are established to ensure that the drug releases in a controlled and predictable manner. They serve as a standard to determine whether a batch of tablets or capsules meets the required dissolution specifications. The acceptance criteria for dissolution typically include the following factors:

1. Dissolution Profile:
   • The test is conducted at specified time intervals (e.g., 5, 10, 15, 30, 60 minutes).
   • The percentage of the drug released at each time point is measured.
2. Specification for Drug Release:
   • The most common acceptance criteria are based on the percentage of the active pharmaceutical ingredient (API) released within a set time. For example, USP often sets the criteria as:
     • Immediate-release dosage forms: 80% of the drug should be released within 30 minutes. This is typically the target for most immediate-release tablets and capsules.
     • Extended-release or controlled-release dosage forms: Specific release profiles are defined based on the product’s characteristics, but often a slower release is required. Criteria might vary depending on the formulation and its intended use.

Acceptance Criteria for Immediate-Release Tablets

For an immediate-release solid dosage form, the USP dissolution test typically has the following acceptance criteria:

• Time 0-30 Minutes: At least 80% of the drug should dissolve within 30 minutes.
  • Example: For a tablet that contains 100 mg of the drug, the test result should show that at least 80 mg has dissolved after 30 minutes.
  This criterion ensures that the drug is released within a predictable and acceptable time frame, making it available for absorption in the body.

Acceptance Criteria for Modified-Release Forms (Extended-Release, Controlled-Release)

Modified-release formulations, such as extended-release (ER) or controlled-release (CR) dosage forms, have specific dissolution requirements due to their unique drug release profiles. These dosage forms are designed to release the drug gradually over a prolonged period.

• Extended-Release (ER): For extended-release tablets or capsules, the dissolution rate is typically slower compared to immediate-release forms. The criteria might specify that the drug should release in a controlled manner over several hours.
  • For example, in some cases, no more than 10-20% of the drug should be released within the first hour, with the remaining percentage to be released progressively over several hours (e.g., 50-70% by 4 hours).
• Controlled-Release (CR): Similar to ER dosage forms but may have more stringent release profiles, requiring a near-zero order release (constant release rate).

Acceptance Criteria (Example from USP for Immediate-Release Dosage Forms)

• For Immediate-Release Tablets:
  • At time 0 (the start of the test), the release of the drug should be minimal or zero.
  • At 30 minutes: 80% of the drug must have dissolved. If 80% of the drug has dissolved, it indicates the tablet or capsule will be absorbed appropriately in the gastrointestinal tract.
  Example of acceptance criteria for the release of a 100 mg drug from a tablet:
  • At 15 minutes: ≥40% dissolved
  • At 30 minutes: ≥80% dissolved
  • At 60 minutes: ≥95% dissolved
  Note: These percentages can vary depending on the specific drug and formulation.

Modified-Release (ER or CR) Dosage Form Example (USP)

• For extended-release tablets, the dissolution criteria might specify:
  • After 1 hour: No more than 10% of the drug should be released.
  • After 2 hours: No more than 20% of the drug should be released.
  • After 4 hours: 50-60% of the drug should be released.
  • After 8 hours: At least 80% of the drug should be released.

These criteria ensure that the dosage form performs as intended by releasing the drug at a steady and controlled rate over time.

Regulatory and Pharmacopeial Standards

• USP (United States Pharmacopeia), BP (British Pharmacopeia), and EP (European Pharmacopeia) provide official dissolution test methods and acceptance criteria.
• Each drug product might have unique dissolution requirements depending on its formulation and therapeutic need, with variations for immediate-release, extended-release, or modified-release products.

Conclusion

Dissolution testing plays a vital role in managing quality of solid oral dosage forms. By accurately measuring the release of the active ingredient from the dosage form, it helps confirm the drug will behave predictably once administered.

FAQS

References

• Dissolution testing
• Resources for dissolution testing