Carbamazepine Co-crystal Screening with Dicarboxylic Acids Co-Crystal Formers

Co-crystal is believed to improve the solubility and
dissolution rates and thus, enhanced the bioavailability of poor water
soluble drugs particularly during the oral route of administration.
With the existing of poorly soluble drugs in pharmaceutical industry,
the screening of co-crystal formation using carbamazepine (CBZ) as
a model drug compound with dicarboxylic acids co-crystal formers
(CCF) namely fumaric (FA) and succinic (SA) acids in ethanol has
been studied. The co-crystal formations were studied by varying the
mol ratio values of CCF to CBZ to access the effect of CCF
concentration on the formation of the co-crystal. Solvent evaporation,
slurry and cooling crystallization which representing the solution
based method co-crystal screening were used. Based on the
differential scanning calorimetry (DSC) analysis, the melting point of
CBZ-SA in different ratio was in the range between 188oC-189oC.
For CBZ-FA form A and CBZ-FA form B the melting point in
different ratio were in the range of 174oC-175oC and 185oC-186oC
respectively. The product crystal from the screening was also
characterized using X-ray powder diffraction (XRPD). The XRPD
pattern profile analysis has shown that the CBZ co-crystals with FA
and SA were successfully formed for all ratios studied. The findings
revealed that CBZ-FA co-crystal were formed in two different
polymorphs. It was found that CBZ-FA form A and form B were
formed from evaporation and slurry crystallization methods
respectively. On the other hand, in cooling crystallization method,
CBZ-FA form A was formed at lower mol ratio of CCF to CBZ and
vice versa. This study disclosed that different methods and mol ratios
during the co-crystal screening can affect the outcome of co-crystal
produced such as polymorphic forms of co-crystal and thereof. Thus,
it was suggested that careful attentions is needed during the screening
since the co-crystal formation is currently one of the promising
approach to be considered in research and development for
pharmaceutical industry to improve the poorly soluble drugs.

• Syarifah Abd Rahim
• Fatinah Ab Rahman
• Engku N. E. M. Nasir
• Noor A. Ramle

• Carbamazepine
• co-crystal
• co-crystal former
• dicarboxylic acid.

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