Recent Innovations in Dissolution Calibration
Mary Oates
Warner-Lambert, Morris Plains, NJ

The requirements for calibration of dissolution baths remained virtually unchanged for many years. However, due to increased focus within the pharmaceutical industry on dissolution calibration, innovative changes have recently been made to the calibration requirements and more have been proposed. The goal of these innovations is to ensure that essential information regarding dissolution bath performance is collected while eliminating those tests that do not provide unique, useful information.

The primary driving force behind these changes has been the PhRMA Subcommittee on Dissolution Calibrators (chaired by Mary Oates), formed in May of 1996 to evaluate alternatives to the existing calibration requirements. The first achievement of the group was a reduction in the required calibrator tablet tests based on a statistical assessment of data generated during three calibrator tablet collaborative studies executed between 1989 and 1994. In fact, 50% of the calibrator tests were eliminated based upon the statistical evidence that these tests did not provide unique information about bath performance. This change became effective with the introduction of Prednisone Lot L and Salicylic Acid Lot N.

More recently, the PhRMA Subcommittee has focused on mechanical calibration as a potential replacement for calibrator tablets. Mechanical calibration can be defined as the measurement of critical physical parameters of the dissolution bath which, when stringently controlled, provide evidence of the proper operation of the apparatus. Although some mechanical calibration is currently performed (e.g., wobble, centering, etc.), the committee's original proposal was to replace the calibrator tablets through use of enhanced mechanical calibration.

A collaborative study executed by PhRMA members to determine the feasibility of this idea demonstrated that the prednisone calibrator (both the current prednisone tablet and the FDA-recommended NCDA2) is operationally sensitive to several critical bath parameters. In addition, it was found that insufficient information exists to establish a meaningful tolerance for vibration.

The overall recommendation of the Subcommittee at this time is to continue the use of a prednisone calibrator (while eliminating the salicylic acid calibrator) and to continue to collect mechanical calibration data. It is particularly important that laboratories begin to collect vibration information using one of the commercially available vibration meters so that a database can be established to assist in defining a relevant tolerance. The complete results and recommendations of the study described above will be published in an upcoming Pharmaceutical Forum article.

Although the idea of stand-alone mechanical calibration has been met with some skepticism, it remains the ultimate goal of the subcommittee. The Subcommittee believes that each of the parameters critical to bath operation can be measured and therefore controlled. Input from industry is now required to assist in furthering the goal.

Please address comments to Mary Oates, Ph.D
email: mary.oates@wl.com
Phone: 973-540-5247
Fax: 973-540-5265