Pharmaceutical Calculation Suite
Verify API release rate from solid dosage forms. Three-stage sampling plan with time-point specific acceptance criteria.
Dissolution Testing in Quality Control
Dissolution testing verifies that a solid dosage form releases its active pharmaceutical ingredient (API) at the required rate under physiological conditions simulated in vitro. USP <711> governs immediate release (IR) product testing and is fundamental to batch release, product development, and regulatory submission.
Key Applications:
The three-stage sampling plan (S1, S2, S3) efficiently evaluates batch conformance while minimizing unnecessary testing of acceptable batches.
Three-Stage Acceptance Criteria
Dissolution testing employs a sequential stage approach where dissolution is evaluated at a single time point (usually the labeled release time) for each stage. The specification Q represents the percentage of API that should be dissolved at that time point.
Stage 1 (S1) — Initial Sample (n=6 vessels):
If all 6 results are ≥ Q+5%, the batch PASSES. If any result is < Q+5%, proceed to Stage 2.
Stage 2 (S2) — Pooled Analysis (n=12 total vessels):
Test 6 additional units (combine with Stage 1 for n=12 total).
If both conditions are met, the batch PASSES. If not, proceed to Stage 3.
Stage 3 (S3) — Extended Analysis (n=24 total vessels):
Test 12 additional units (combine with Stages 1 and 2 for n=24 total).
If all three conditions are met, the batch PASSES. If any condition fails, the batch FAILS and requires investigation.
Typical Specifications for Immediate Release:
| Time Point | Typical Q Value | Purpose |
|---|---|---|
| 15 min | 20–30% | Rapid disintegration check |
| 30 min | 40–80% | Primary time point (most common) |
| 45 min | 60–80% | Secondary time point |
| 60 min | 70–85% | Extended release verification |
Dissolution Testing Parameters
| Symbol | Parameter Name | Units | Description |
|---|---|---|---|
| Q | Dissolution Specification | % Released | Target percentage of API dissolved at the specified time point. Set per product monograph (typically 75–85% at primary time point). |
| n | Number of Vessels/Units | vessels | Stage 1: n=6; Stage 2: n=12 (cumulative); Stage 3: n=24 (cumulative). |
| Individual Dissolution | Individual Unit Result | % Released | Dissolution value for each vessel, expressed as percentage of label claim released at the time point. |
| Average Dissolution | Mean Dissolution | % Released | Arithmetic mean of all n individual results at the time point. |
| Stage | Testing Phase | S1/S2/S3 | Stage 1, 2, or 3 of the sequential sampling plan. Each stage has distinct acceptance criteria. |
Worked Example with Immediate Release Tablet
Scenario: A pharmaceutical manufacturer is conducting batch release dissolution testing for an immediate release tablet containing 200 mg ibuprofen. Dissolution is tested at 30 minutes in water pH 7.4 at 37°C using USP Apparatus II (paddle). The product specification is Q = 80% at 30 minutes.
Alternative Scenario (if Stage 1 failed): If one vessel in Stage 1 had returned 82% (below 85%), the batch would not pass Stage 1 and would proceed to Stage 2 with 6 additional vessels (n=12 total). The Stage 2 criterion requires the average of all 12 units ≥ 80% (Q) and no unit < 65% (Q − 15%).
Interpretation: The batch demonstrates excellent and consistent API release with all individual results exceeding the lower bound specification, indicating robust formulation performance and manufacturing consistency.
↪ Open Dissolution IR Calculator