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    • The synthesis of modified polymer

    2020-07-27

    The synthesis of modified polymer (PBI-adenine) is presented elsewhere [28] and the current study is focused on exploring the capability of this innovative material to remove a broad range of DNA alkylating agents from API organic solvent solutions, identify limitations for the use of PBI-adenine for API degenotoxification and, to define strategies and operation conditions at which PBI-adenine can successfully remove GTIs down to TTC values, with minimal API losses.
    Experimental
    Results and discussion
    Conclusions The potential development of a versatile material able to scavenge a broad range of DNA alkylating agents from organic solvent based solutions was investigated. Adsorption of GTIs from different chemical families, on an ampk inhibitors modified PBI polymer, was found to be effective (> 80%) at room temperature. Our results show that in a typical industrial scenario, where the GTI is present in low concentration compared to the API, the efficiency and GTI removal rate can be improved with temperature increase. Furthermore, a simple solvent washing step was implemented to recover the API trapped in PBI-adenine polymer without GTI back contamination, exploring the fact that, the GTI is not easily retrieved from the adsorbing platform. Based on these achievements, a strategy is proposed for the efficient removal of a DNA alkylating GTI from an API solution in an organic solvent, leading to GTI to API ratios within the limits imposed by legislation, as low as 0.6 mg GTI/g API with only a 3.5% loss of API for the worst-case scenario considered. From the point of view of an industrial application this is a major advantage, since with one simple washing step lymph could be possible to recover the API, minimizing its loss, addressing the economic impact for the pharmaceutical companies associated with API losses in time consuming and material demanding elaborated purification strategies.
    Data availability statement
    Acknowledgements The authors acknowledge dedicated funding from Fundação para a Ciência e Tecnologia (FCT) through the Project SelectHost (PTDC/QEQ-PRS/4157/2014) and iBB-Institute for Bioengineering and Biosciences (UID/BIO/04565/2013), from Programa Operacional Regional de Lisboa 2020 (Lisboa-01-0145-FEDER-007317) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – Brasil). We thank to Hovione PharmaScience Ltd. for supplying APIs and technical know-how.