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Influence of Microenvironment pH, Humidity, and Temperature on the Stability of Polymorphic and Amorphous Forms of Clopidogrel Bisulfate

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Abstract

The effect of microenvironment pH, humidity, and temperature was evaluated on the stability of polymorphic and amorphous forms of clopidogrel bisulfate, when present alone or in combinations. Oxalic acid and sodium carbonate were used as solid stressors to create acidic and alkaline pH, respectively. The samples without and with stressors were subjected for 3 months to (1) 0% RH, 25% RH, 75% RH, and 85% RH at 40°C and also to (2) 60°C, 80°C, and 100°C at 0% RH. In case of solid samples without stressors, the mixture of polymorphic and amorphous forms showed more degradation than the individual forms above critical relative humidity (85% RH). Similar higher degradation was observed between 75% RH and 85% RH in case of acid-stressed samples. In alkaline microenvironment, all the samples showed identical decomposition attributed to conversion of bisulfate salt to free base. Thermal studies indicated that polymorphic forms of clopidogrel bisulfate and also its glassy amorphous form were highly resistant to temperature, whereas the rubbery state of the drug degraded significantly at temperatures of ≥80°C.

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Acknowledgement

The authors would like to thank TA instruments, Bangaluru, India for providing facilities to perform vapor sorption analysis.

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Authors and Affiliations

  1. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062, Mohali, Punjab, India

    Dhara K. Raijada & Saranjit Singh

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062, Mohali, Punjab, India

    Arvind K. Bansal

Authors
  1. Dhara K. Raijada
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  2. Saranjit Singh
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  3. Arvind K. Bansal
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Correspondence to Saranjit Singh.

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Raijada, D.K., Singh, S. & Bansal, A.K. Influence of Microenvironment pH, Humidity, and Temperature on the Stability of Polymorphic and Amorphous Forms of Clopidogrel Bisulfate. AAPS PharmSciTech 11, 197–203 (2010). https://doi.org/10.1208/s12249-010-9376-1

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  • DOI: https://doi.org/10.1208/s12249-010-9376-1

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