As the demand for new drugs is rising, the pharmaceutical industry faces the quest of shortening development time, and thus, reducing the time to market. Environmental aspects typically still play a minor role within the early phase of process development. Nevertheless, it is highly promising to rethink, redesign, and optimize process strategies as early as possible in active pharmaceutical ingredient (API) process development, rather than later at the stage of already established processes. The study presented herein deals with a holistic life-cycle-based process optimization and intensification of a pharmaceutical production process targeting a low-volume, high-value API. Striving for process intensification by transfer from batch to continuous processing, as well as an alternative catalytic system, different process options are evaluated with regard to their environmental impact to identify bottlenecks and improvement potentials for further process development activities.
Structured catalyst has been developed for C−C triple bond three-phase hydrogenation. The sintered metal fiber (SMF) coated by different oxides served as support for monodispersed Pd nanoparticles (6.4 ± 0.5 nm). The effect of acid−base properties and reducibility of metal oxide coating on catalytic performance in the liquid phase (T = 303− 348 K; P = 1−20 bar) hydrogenation of 2-butyne-1,4-diol to 2-butene-1,4-diol (B2) has been studied. The oxides MgO, ZnO, Ga 2 O 3 , Al 2 O 3 , ZrO 2 , SnO 2 , and SiO 2 and the mixtures of MgO + ZnO + Al 2 O 3 , MgO + Al 2 O 3 , and ZnO + Al 2 O 3 were tested. The catalyst activity was higher up to 10-fold for Pd 0 on acidic supports, like SiO 2 , but demonstrated lower selectivity to B2 as compared to the basic oxides. The highest yield (∼99%) of the target B2 and stability over four consecutive runs were attained over the 0.2% Pd 0 /ZnO/SMF catalyst. The high selectivity to B2 was attributed to the formation of an active phase containing intermetallic PdZn alloy as confirmed by XPS. The reaction kinetics was modeled using a Langmuir−Hinshelwood mechanism and found consistent with the experimental data. The developed structured catalyst is suitable for a design of flow multiphase reactors to perform alkyne semihydrogenations in continuous mode.
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