10.1021/acs.molpharmaceut.7b00092.s001 Ewa Skorupska Ewa Skorupska Sławomir Kaźmierski Sławomir Kaźmierski Marek J. Potrzebowski Marek J. Potrzebowski Solid State NMR Characterization of Ibuprofen:Nicotinamide Cocrystals and New Idea for Controlling Release of Drugs Embedded into Mesoporous Silica Particles American Chemical Society 2017 BA MCM -41 walls MSP pores MAS API Mesoporous Silica Particles Grinding magic angle 15 N spectra Thermal solvent-free Controlling Release benzoic acid MSP pore TSF method NMR results MCM -41 mesoporous silica particle NA components 1 H IBU 13 C Solid State NMR Characterization NMR spectroscopy SS NMR 60 kHz 2017-04-12 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Solid_State_NMR_Characterization_of_Ibuprofen_Nicotinamide_Cocrystals_and_New_Idea_for_Controlling_Release_of_Drugs_Embedded_into_Mesoporous_Silica_Particles/4884800 Grinding and melting methods were employed for synthesis of pharmaceutical cocrystals formed by racemic (R/S) and entiomeric (S) ibuprofen (IBU) and nicotinamide (NA) as coformer. Obtained (<i>R</i>/<i>S</i>)-IBU:NA and (<i>S</i>)-IBU:NA cocrystals were fully characterized by means of advanced one- and two-dimensional solid state nuclear magnetic resonance (SS NMR) techniques with very fast magic angle spinning (MAS) at 60 kHz. The distinction in molecular packing and specific hydrogen bonding pattern was clearly recognized by analysis of <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N spectra. It is concluded from these studies that both methods (grinding and melting) provide exactly the same, specific forms of cocrystals. Thermal solvent-free (TSF) approach was used for loading of (<i>R</i>/<i>S</i>)-IBU:NA and (<i>S</i>)-IBU:NA into the pores of MCM-41 mesoporous silica particle (MSP). The progress and efficiency of this process was analyzed by NMR spectroscopy. It has been confirmed that TSF method is an effective and safe technique of filling the MSP pores with active pharmaceutical ingredients (APIs). By analyzing the NMR results, it has been further proved that excess of IBU and NA components, which are not embedded into the pores during melting and cooling, crystallize on the MCM-41 walls preserving very specific arrangement, characteristic for crystalline samples. By investigating kinetic of release for (<i>R</i>/<i>S</i>)-IBU/MCM-41, (<i>S</i>)-IBU:NA/MCM-41, and (<i>R</i>/<i>S</i>)-IBU:NA/MCM-41 samples containing active components exclusively inside of the pores, it was revealed that release of IBU is much faster for the first of the samples compared to those containing IBU and NA inside the pores. The hypothesis that the rate of release of API can be controlled by specific composition of cocrystal embedded into the MSP pore was further supported by study of (<i>R</i>/<i>S</i>)-IBU:BA/MCM-41 sample with benzoic acid (BA) as coformer.