A Compliance Perspective on Dissolution Method Validation for Immediate-Release Solid Oral Dosage Forms on Automated Instrumentation - Pharmaceutical Technology

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A Compliance Perspective on Dissolution Method Validation for Immediate-Release Solid Oral Dosage Forms on Automated Instrumentation
An automated dissolution method can be a powerful tool to test drug products at all phases of their development. With minimal automated method validation, this tool can be used early in the drug-evaluation process. And with additional validation efforts, an automated method can be extended to the testing of Phase IV stability batches. Validating an automated dissolution-test method requires an understanding of the potential effects from filtration parameters, system interference, carry-over, cleaning..

Pharmaceutical Technology

Calibration checks. A periodic calibration schedule must be established for each component on the automated system. The schedule may include semiannual, quarterly, weekly, and daily activities designed to confirm the proper operation of the system. For the automated dissolution-testing system, the quarterly activities may include balance and temperature-probe calibrations. In addition, weekly or daily calibrations may include a quick balance check. For the dissolution apparatus, a semiannual performance calibration must be completed using USP calibrators. Trial dissolutions must be performed on disintegrating (e.g., prednisone) and nondis-integrating (e.g., salicylic acid) USP calibrators. Each dissolution test must pass the USP acceptance criteria established for the lot of drug tested. Semiannual physical testing must also pass USP acceptance criteria. The physical specifications include shaft and basket eccentricities, bath level, shaft verticality, and vessel and shaft centering. In addition, even though USP acceptance criteria have not yet been established for vibration, bath vibration is an important variable that should be measured periodically, especially if mechanical components have been changed on any of the components of the automated system. New mechanical components may increase bath vibration, which may increase dissolution results inaccurately. Daily physical specifications that must pass USP acceptance criteria include proper paddle–basket height, initial and final temperatures in all vessels, and shaft rotational speed (rpm).


Automated instrumentation for dissolution testing offers several advantages such as the ability to perform unattended testing and the ability to screen several batches with varying parameters. But, automated instrumentation also poses challenges for a dissolution chemist, including the need to have an overall understanding of the the automated system. Parameters such as filtration, system interference, carry-over, cleaning parameters, and media replacement are factors that must be addressed and validated to ensure equivalent results are obtained with manual and automated methods. The automated system can be used to generate GMP data only if all components on or supporting the system maintain a documented and current qualification and calibration status.


The author thanks Ron Mamajek, John Ballard, Ronnie McDowell, Dr. Michael Breslav, Dr. Daniel Kroon, Dr. Weiyong Li, and Dr. Brigitte Segmuller for their valuable suggestions.


1. "<1092> The Dissolution Procedure: Development and Validation," Pharmacopeial Forum, 30 (1), 351–363 (Jan.–Feb. 2004).

2. "<1092> The Dissolution Procedure: Development and Validation," Pharmacopeial Forum, 31 (5), 1463–1475 (Sep.–Oct. 2005).

David Fortunato is a scientist in the Chem Pharm division of Analytical Development, US, Johnson and Johnson Pharmaceutical Research and Development, LLC, Welsh and McKean Rds., Spring House, PA 19477, tel. 215.628.5098, fax 215.540.4684,

Submitted: Feb. 22, 2006. Accepted: Apr. 7, 2006.

Keywords: Analytical testing, process automation, regulation validation and compliance, solid dosage forms


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