API Form & Drug product research

Published by ndt228 on 21 November 2012 - 1:27pm


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This thread starteded as a place to locate anything related to the final API form(s) in which PZQ might be isolated (ie Drug Substance), or the formulation of these into Drug Product.


ndt228's picture

Here is a link to a recent paper in Crystal Growth & Design:
This details co-crystallisation of PZQ with a variety of organic di-acids, and single-crystal x-ray analysis of their structures.  Such crystals are of potential use in formulation as they often alter the solubility and dissolution properties of the API.  NB co-crystals are formed despite the inability to create a true salt of PZQ. 
Interestingly, the crystallographic study showed that there are two main rotational conformers for PZQ, which differ in the configuration of the C=O groups in the piperazinone-cyclohexylcarbonyl segment.  In rac-PZQ crystals (ie not a co-crystal) a syn-conformation is seen, whereas for all but one co-crystals it is anti-.  Reference is also made to (R)- and (S)- PZQ crystals as being hemi-hydrates, and also showing anti- configuration.
The chiral di-acids named in the abstract were all simple homologs of succinic acid or unsaturated equivalents.  No mention was made of any chiral acids being trialled.  It might in theory be possible to achieve a resolution by co-crystallisation despite the inability to form a salt !
regards, Nick

If a DKR version of this process could be developed (or even using it as it is) there would be no waste in producing (R)-Praziquantel.
DOI: 10.1021/op300343q