A new approach to “abnormal dissolution profile” problems for extended release drug products

Bar Edelshtein, Analytical Development, Global R&D, Teva Pharmaceuticcal Industries, Ltd., Kfar Saba, Israel (Bar.Edelshtein@teva.co.il)

Behavior of certain drug products in dissolution profile testing, in several cases, when the profile is especially long, may exhibit abnormal profile: sometimes, in a specific sampling point, drug release may be unexpectedly lower than in a previous. This may affect release rate of API from a dosage form. Such a behavior is often characteristic for API’s which have limited stability in aqueous solutions due to functional groups susceptible for hydrolysis.

Moreover, this may be followed by emerging of unknown impurities / degradation products. Reliable quantitation in such cases is usually problematic, especially when relative response factors (RRF) for emerging impurities has not been yet determined, or it is impossible for several reasons.

Our attitude in using diverse analytical tools (compatibility of materials, chromatographic, spectral, protection from environment influence, etc.) will be presented, to monitor and control such degradation processes, if occur.

One of the applied tools is the “Isosbestic point evaluation” approach. Wavelength of HPLC method is chosen to represent the same (or most similar) extinction coefficient for API and its degradation product(s). As a result, degradation, or increase of impurities during stability studies of extended release products, can be reliably assessed.

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Abstract Reference & Short Personal Biography of Presenting Author

Bar Edelshtein is Analytical Project Coordinator at Global R&D, Teva Pharmaceuticals, Ltd. He is responsible for developing analytical methods for small molecules API and drug products in generic development and NTE at Kfar-Saba R&D site. Bar has joined Teva in 2008 and he involved in development of wide range of generic products and complex projects utilizing various analytical methods and technologies.

Bar holds a B.Sc. degree in Biotechnology engineering from Ort Braude College of Engineering, Carmiel, Israel.