Calibration of the dissolution test apparatus is a critical requirement in pharmaceutical quality control to ensure the accuracy and reliability of drug release data. Historically, two standards were used: Prednisone (disintegrating) and Salicylic Acid (non-disintegrating).
However, since 2009, the landscape of USP calibration has shifted significantly. This article explores why Salicylic Acid was withdrawn and what the current regulatory standards require.
The History of Dissolution Calibration Standards
For years, the USP General Chapter <711> Dissolution mandated the use of Performance Verification Testing (PVT) using two distinct types of tablets:
- Prednisone Tablets USP: Representing a disintegrating formulation. These tablets break down into smaller particles, testing the apparatus's sensitivity to physical variables like vibration and flow patterns.
- Salicylic Acid Tablets USP: Representing a non-disintegrating formulation. These tablets dissolve slowly from a constant surface area, testing the chemical and temperature consistency of the medium.
The Regulatory Shift: USP and FDA Changes
In late 2009 and early 2010, the pharmaceutical industry saw a major update in how dissolution apparatuses were validated:
- December 01, 2009: The USP officially withdrew the Salicylic Acid calibration requirement.
- January 2010: The FDA published updated cGMP guidelines regarding the calibration of dissolution apparatus.
- March 2010: The USP released a comprehensive Mechanical Calibration Toolkit. This toolkit transitioned the focus primarily to Prednisone tablets for Performance Verification Testing (PVT) alongside stricter mechanical checks.
Why was Salicylic Acid Withdrawn?
While the USP and FDA did not issue a singular, formal "requirement for change" statement, the pharmaceutical community recognizes several technical and practical reasons for the removal of Salicylic Acid.
1. Lack of Practical Relevance
Salicylic Acid tablets are non-disintegrating and uncoated. In modern pharmaceutical manufacturing, formulations that are both uncoated and non-disintegrating are extremely rare. Since the goal of calibration is to mimic real-world conditions, maintaining a standard for a tablet type that is rarely produced became unnecessary.
2. Physical Instability and Quality Issues
Salicylic Acid tablets faced significant "quality of standard" challenges:
- Sticking: The tablets had a tendency to stick together in storage.
- Instability: They were sensitive to environmental factors, which led to inconsistent results that did not necessarily reflect the performance of the dissolution apparatus itself.
- Analytical Standards: These physical defects violated the strict requirements for an analytical standard, making them unreliable for precise calibration.
Current Status of Calibration
Today, the Performance Verification Test (PVT) is conducted using USP Prednisone Tablets only. The focus has shifted toward a "Mechanical Calibration" approach, where the physical dimensions and alignment of the apparatus (shaft wobble, centering, paddle depth, and vibration) are monitored more strictly.
Key Takeaways for Lab Managers:
- Always use the USP Toolkit: Ensure your SOPs reflect the March 2010 USP updates.
- Focus on Prednisone: Prednisone remains the gold standard for detecting "disturbances" in the dissolution environment.
- Mechanical Integrity: Proper mechanical calibration is now considered just as vital as the chemical tablet test.
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