Enhancing the Pharmaceutical Properties of Ibuprofen through Spherical Agglomeration-Co-Crystallization with Nicotinamide: A Comprehensive Study of Micromeritic, Tabletability, and Dissolution Characteristics
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Abstract
Developing efficient methods for cocrystal production is crucial to improving drug solubility
and bioavailability. This study utilized the spherical agglomeration-co-crystallization (SA-CC)
method to produce spherical ibuprofen-nicotinamide (IBU-NICO) cocrystals. This method used
ethanol (ETA) as a solvent and a mixture of deionized water and PEG-4000 as an anti-solvent,
enhancing the micromeritic properties of the cocrystal. The addition of dichloromethane (DCM)
facilitated the formation of spherical particles via rapid viscous phase transition. Fouriertransform infrared (FTIR) spectroscopy identified significant molecular interactions, such as
hydrogen bonding between the ibuprofen carboxyl and nicotinamide acylamino groups, ensuring
cocrystal stability. Hot-stage microscopy (HSM) and scanning electron microscopy (SEM)
analyses demonstrated that cocrystals exhibited lower thermal stability but improved dissolution
rates due to their amorphous-crystalline structures and rough, porous surfaces. Differential
scanning calorimetry (DSC) showed altered thermal profiles with a reduction of 7.21oC,
indicating modified crystal lattice structures. Powder X-ray diffraction (PXRD) confirmed the
creation of new crystalline phases. Micromeritic evaluations revealed favorable particle size
distribution (PSD) with an average size of 5 mm, enhanced flowability, and compressibility,
with cocrystals showing superior tensile strength (2.36 MPa at 207.97 MPa) and dissolution
rates 2.82 times higher than pure IBU at pH 6.8. These findings highlight the potential of the
SA-CC method to produce cocrystals with enhanced drug properties, paving the way for
improved pharmaceutical formulations.
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