The intrinsic photostability characteristics of new drug substances should be evaluated to demonstrate that, as appropriate, light exposure does not result in unacceptable change. A guideline on Stability Testing of New Drug Substances and Products addressing the recommendations for photostability testing has been published by the ICH Organization. Developing or manufacturing pharmaceutical drugs, a robust photostability testing process is essential to ensure product quality and regulatory compliance. For drug substances, photostability test should consist of two parts: Forced degradation testing and Confirmatory testing. The purpose of forced degradation testing studies is to evaluate the overall photosensitivity of the material for method development purposes and degradation pathway elucidation. This testing may involve the drug substance alone or in matrix. In these forced degradation studies, a variety of exposure conditions may be used, depending on the photosensitivity of the drug substance involved and the intensity of the light sources used. This information may be useful in developing and validating suitable analytical methods. Confirmatory studies should then be undertaken to provide the information necessary for handling, packaging, and labeling. For companies it is important to know the real degradation time of the drugs when they are exposed to the solar light. Nevertheless, the sun irradiation intensity is never constant and it changes significantly according to the seasons, the place and the atmospheric conditions. Therefore, the results from the stress tests should be correlated with the virtual degradation times occurring in natural degradation conditions. A multivariate method, based on PCR (Principal Component Regression) and PLS (Partial Least Squares) modelling, was defined able to extrapolate a real drug degradation from a forced degradation test. The model was built on a series of three photo-sensitive drugs, Nitrofurazone, Melatonin and Amiloride, submitted to light exposure under both sun and artificial source. PLS MODEL: log deg% = a T + b L/W E + c where a, b and c are the regression coefficients, T is the exposure time, L is the lux value, W is the light power and E is the absorbed energy. The main parameters of the natural light, namely illuminance (lux) and irradiation power (W/cm2), have been monitored along a three-year period. A so long monitoring time to obtain reliable mean irradiation characteristics was necessary because the high variance of the atmospheric conditions and the different light intensity throughout day. 1. International Conference on Harmonization, "Guidelines for the Photostability Testing of New Drug Substances and Products" Federal Register 1997, 62, 27115-27122 Washington. 2. S.R. Thatcher, Pharmaceutical Technology 2001, 25, 231-239.

A CHEMOMETRIC MODEL FOR ASSESSMENT OF REAL DRUG PHOTODEGRADATION FORM FORCED TEST

DE LUCA M;IOELE, Giuseppina;RAGNO G.
2008

Abstract

The intrinsic photostability characteristics of new drug substances should be evaluated to demonstrate that, as appropriate, light exposure does not result in unacceptable change. A guideline on Stability Testing of New Drug Substances and Products addressing the recommendations for photostability testing has been published by the ICH Organization. Developing or manufacturing pharmaceutical drugs, a robust photostability testing process is essential to ensure product quality and regulatory compliance. For drug substances, photostability test should consist of two parts: Forced degradation testing and Confirmatory testing. The purpose of forced degradation testing studies is to evaluate the overall photosensitivity of the material for method development purposes and degradation pathway elucidation. This testing may involve the drug substance alone or in matrix. In these forced degradation studies, a variety of exposure conditions may be used, depending on the photosensitivity of the drug substance involved and the intensity of the light sources used. This information may be useful in developing and validating suitable analytical methods. Confirmatory studies should then be undertaken to provide the information necessary for handling, packaging, and labeling. For companies it is important to know the real degradation time of the drugs when they are exposed to the solar light. Nevertheless, the sun irradiation intensity is never constant and it changes significantly according to the seasons, the place and the atmospheric conditions. Therefore, the results from the stress tests should be correlated with the virtual degradation times occurring in natural degradation conditions. A multivariate method, based on PCR (Principal Component Regression) and PLS (Partial Least Squares) modelling, was defined able to extrapolate a real drug degradation from a forced degradation test. The model was built on a series of three photo-sensitive drugs, Nitrofurazone, Melatonin and Amiloride, submitted to light exposure under both sun and artificial source. PLS MODEL: log deg% = a T + b L/W E + c where a, b and c are the regression coefficients, T is the exposure time, L is the lux value, W is the light power and E is the absorbed energy. The main parameters of the natural light, namely illuminance (lux) and irradiation power (W/cm2), have been monitored along a three-year period. A so long monitoring time to obtain reliable mean irradiation characteristics was necessary because the high variance of the atmospheric conditions and the different light intensity throughout day. 1. International Conference on Harmonization, "Guidelines for the Photostability Testing of New Drug Substances and Products" Federal Register 1997, 62, 27115-27122 Washington. 2. S.R. Thatcher, Pharmaceutical Technology 2001, 25, 231-239.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/187532
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