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Navigating Dissolution Testing in IR Dosage Form

Introduction: Dissolution testing is a crucial aspect of pharmaceutical quality control, drawing the interest of many professionals in the field. In this blog, we'll delve into the various options available when dissolution results fail to meet acceptance criteria at different stages. Let's explore the steps to take when faced with this challenge. The dissolution for Immediate Release (IR) dosage form can be carried through three stages- S1, S2, and S3.

Stage 1 (S1)- Initial Dissolution Testing: Suppose you have a dissolution specification of not less than 85% for an immediate release dosage form, typically referred to as "Q." At stage 1 (S1), you conduct dissolution testing on six individual units, with the expectation that each unit's result should be greater than or equal to Q + 5%, which is 90% in this scenario.

Possibility 1: All six units pass the S1 stage, with results exceeding Q + 5%. In this case, there's no need to proceed to stage 2 (S2). T

he product can be released as it meets the dissolution acceptance criteria at S1.

Possibility 2: If one unit falls short of Q + 5%, let's say 78%, you must move on to stage 2 (S2). However, before proceeding, consider examining the product history to ensure that the 78% result wasn't due to an analytical error. It's always best to preserve the S1 stage analytical solutions for a thorough investigation.

At S2, if all results comfortably meet the specification, there's no need to go to stage 3 (S3). The product can be released.

Stage 2 (S2)- Intermediate Dissolution Testing: At S2, you conduct dissolution testing on an additional six units, resulting in a total of 12 units. The average of these 12 units should be equal to or greater than Q (in this case 85%) without any unit falling below Q - 15% (in this case 70%).

Possibility 1: If all 12 (S1 and S2) results meet the specification, there's no need to continue to S3 testing.

Possibility 2: If one unit fails to meet the S2 criteria, such as yielding 68% instead of the required 85%, you must proceed to stage 3 (S3). Again, investigate the product history and consider raising a significant change if necessary.

Stage 3 (S3) - Final Dissolution Testing: At S3, you conduct dissolution testing on an additional 12 units, totaling 24 units. The acceptance criteria for S3 are an average of 24 units equal to or greater than Q (85%), with no more than two units falling below Q - 15% (70%) and none below Q - 25% (60%).

Possibility 1: If all S1, S2, and S3 (6+6+12 unit results) results meet the specification, the product can be released.

Possibility 2: If one unit fails to meet the S3 criteria, such as reaching only 55% instead of the required 60%, the product does not meet the acceptance criteria even at S3. In this case, you should raise an out-of-specification (OOS) and thoroughly investigate. Retesting beyond S3 is not permitted for dissolution testing. If no lab error is identified and the product fails to meet the criteria, you'll have to reject the batch and investigate the manufacturing process and product history.

Conclusion: This approach to dissolution testing is not only applicable to immediate-release dosage forms but also to extended and delayed-release forms. For products with gelatin components, there is guidance available for repeating dissolution testing using enzymes. It's important to remember that dissolution failure is only considered after a product has failed at S3. Failures at S1 or S2 are not indicative of dissolution specification failure unless S3 results don't meet the criteria.

I hope this blog has shed light on the steps to take when faced with dissolution testing challenges in pharmaceutical quality control.

Please share your thoughts in the comment section below. Thank you for reading!

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