What is "Q" and “Q+5%” in Dissolution

Drug dissolution is a critical attribute of any pharmaceutical product, and it plays a vital role in setting product specifications. The term "Q" is commonly used to express these specifications, and in this article, we will delve into the significance of "Q" and how it is used in designing these specifications.

Introduction:

Hello, I'm Bhaskar Napte, the founder of Pharma Growth Hub. In this article, we'll explore the concept of "Q" and its role in pharmaceutical dissolution specifications.

Defining "Q":

To understand "Q," let's refer to official pharmacopoeias. In the United States Pharmacopeia (USP) General Chapter 711, "Q" is defined as the amount of dissolved active ingredient specified in an individual monograph, expressed as a percentage of the labeled content of the dosage unit. In essence, "Q" represents the percentage of the active pharmaceutical ingredient (API) dissolved during the dissolution process.

In the context of the European Pharmacopoeia (EP), General chapter 2.9.3, the definition of "Q" remains consistent. It is the specified amount of dissolved active substance expressed as a percentage of the labeled content. This underscores the importance of expressing dissolution in terms of percentages.

Calculating "Q" Values:

Dissolution specifications are not typically set at a single step. For immediate-release dosage forms, they may be defined at three different stages (S1, S2, S3), or for modified-release dosage forms, at L1, L2, and L3. Let's examine how "Q" values are calculated using an example.

Assuming our "Q" value is set at 85%, here's how acceptance criteria would be determined at each stage:

1) S1 Stage:

• Six units need to be tested.

• Acceptance criteria: All six units must have dissolution results greater than "Q" + 5%. In this case, that would be 90%. If all units meet this criterion, the product complies with the specification at S1.

2) S2 Stage:

• If one or two units fail at S1, an additional six units are tested.

• Acceptance criteria: The average of all 12 units (6 from S1 and 6 from S2) should be equal to or greater than "Q" (85%). Individual units can be lower, but none should fall below "Q" - 15%, which in this case is 70%.

3) S3 Stage:

• If any units fail at S2, 12 more units are tested, totaling 24 units (S1 + S2 + S3).

• Acceptance criteria: The average of all 24 units should be equal to or greater than "Q" (85%). Similar to S2, not more than two units should fall below "Q" - 15%, and none should be less than "Q" - 25%

Why the "+5%" at S1 Stage:

At the S1 stage, the "+5%" is added to the "Q" value to ensure stringent criteria are met. This adjustment is necessary because, during S1, only six units are tested, providing limited statistical confidence. As we move to S2 and S3 stages with larger sample sizes (12 and 24 units, respectively), we can rely more on the "Q" value itself, as statistical confidence increases.

Conclusion:

Understanding "Q" in dissolution specifications is crucial for ensuring the quality and effectiveness of pharmaceutical products. The multi-stage approach allows for a comprehensive assessment of dissolution performance, taking into account statistical confidence and ensuring product compliance with established standards.

I welcome your thoughts and comments on this important aspect of pharmaceutical quality. Thank you for reading.