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bioRxiv · 10.1101/2023.09.08.556876

Development and Characterization of Co-crystals Assisted with In-silico Screening for Solubility and Permeability Enhancement of Curcumin

Singh, M.·Takawale, S.·Patil, R.·Chaudhari, S.·Pathan, A.·Sangshetti, J.·Moin, A. T.·Zubair, T.·Uddin, M. H.
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Abstract

Despite being a promising phytochemical, Curcumins potential applications are limited due to its classification in BCS class IV, which is associated with low water solubility and permeability. Enhancing the bioavailability of BCS class IV drugs presents a significant challenge, but crystal chemistry provides a hopeful avenue for overcoming this hurdle. In this research, co-crystals of Curcumin were developed to improve both solubility and permeability. Unlike traditional methods that require extensive trial-based lab work and time-consuming screening of co-formers, the use of molecular docking in In-silico co-former screening offers a scientific and rational approach to selecting suitable partners. In this study, two distinct co-crystals were synthesized using a solvent evaporation technique with methanol as the solvent, employing a 1:1 molar ratio. L-proline and piperine were chosen as co-formers to enhance solubility and permeability, respectively. The co-crystals underwent optimization and characterization through Design of Experiments (DOE). Comparing the dissolution study results for the same curcumin concentration, the cumulative drug release (CDR) after 8 hours was 20% for pure curcumin and an impressive 71% for curcumin-L-proline co-crystals. The permeability study, conducted over four hours using the everted gut sac method in phosphate buffer pH 6.8, revealed curcumins permeability to be less than 0.05 mg/mL, while curcumin-piperine co-crystals exhibited a five-fold increase (0.2545 mg/mL) in permeability. The co-crystals formed through a molecular ratio of 1:1 for curcumin-L-proline to enhance solubility and 1:1 for curcumin-piperine to enhance permeability, both demonstrated positive outcomes with support from optimization analysis, FTIR, DSC, SEM, PXRD analysis, and dissolution studies.

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Singh, M., Takawale, S., Patil, R., Chaudhari, S., Pathan, A., Sangshetti, J., Moin, A. T., Zubair, T., Uddin, M. H.. 2023-09-12. Development and Characterization of Co-crystals Assisted with In-silico Screening for Solubility and Permeability Enhancement of Curcumin. https://doi.org/10.1101/2023.09.08.556876

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