Research Interests
Chirality is well known to chemists and has numerous implications, especially in the pharmaceutical industry. Chiral objects cannot be mapped to their mirror image by rotations and translations alone and this is often the case for drugs that come from natural sources; they are found as single enantiomers, rather than as equimolar mixtures of two enantiomers (racemates). Until 2011 many enantiopure blockbuster drugs resulted from “chiral switches” of already existent racemates, but nowadays most of the newly introduced drugs are manufactured as de novo single enantiomers. Since the human body itself is an asymmetric chemical environment (most hormones, enzymes and DNA are chiral), the two enantiomers have often different biological activities and usually only one enantiomer has the desired therapeutic effect (eutomer).
This crucial effect of chirality on the human body led regulatory bodies, such as European Medicines Agency (EMEA) to exercise pressure on the companies to produce enantiopure drugs and to treat the undesired enantiomers as impurities. In turn, the tendency of producing enantiopure drugs has led to the need for designing new and cost-efficient processes to separate enantiomers. Crystallization-based processes are the most widely used methods for the separation of enantiomers], but they are limited to maximum 50% yield of the preferred enantiomer.
Viedma Ripening
Several years ago, Viedma discovered experimentally that a racemic mixture of conglomerate crystals of the achiral NaClO3 in contact with their saturated solution, subjected to attrition, can undergo complete deracemization. The process is believed to be of utmost importance, as it is carried out at low temperatures –isothermal conditions- and low supersaturation levels, where nucleation is not probable to occur.
I have conducted both experimental and modelling work in this field in order to understand the main interplay among the sub-mechanisms and optimize the process.
Temperature Cycling
An alternative and promising method to Viedma Ripening, that still, maintains high yield is temperature cycling-enhanced- deracemization. According to this technique, a racemic suspension of a conglomerate forming system undergoes symmetry breaking under periodic change of temperature, rather than grinding. This process, is cheaper, more efficient and faster than Viedma Ripening. Its main disadvantage is the higher possibility of nucleation, event that compromises chiral purity.
I have performed modelling work, that describes the possible interplay among mechanisms that probably take place in this process.
Population Balance Modelling
Population Balances are deterministic formulations that are able to describe the dynamics of a system of particles that undergo growth, dissolution, breakage, agglomeration, racemization etc. Such models typically consist of partial Integro-differential equations (PIDE) able to map the evolution of population, coupled with ordinary differential equations in order to describe other phenomena, such mass balances etc.
In my research I have created PBMs for Viedma Ripening, Temperature Cycling, Breakage processes etc. in order to identify the main mechanisms and driving forces behind the processes.
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