Solid State NMR Characterization of Ibuprofen:Nicotinamide Cocrystals and New Idea for Controlling Release of Drugs Embedded into Mesoporous Silica Particles

Abstract

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 (R/S)-IBU:NA and (S)-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 H,C, and 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 (R/S)-IBU:NA and (S)-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 (R/S)-IBU/MCM-41, (S)-IBU:NA/MCM-41, and (R/S)-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 (R/S)-IBU:BA/MCM-41 sample with benzoic acid (BA) as coformer.

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

“…When indomethacin was incorporated into the functionalized SBA-15 matrix, drug-matrix interactions were enhanced. Skorupska et al used advanced SS MAS experiments to analyze other systems of pharmaceutical co-crystal loaded into mesoporous silica [202,203]. The authors used very fast MAS NMR, 1 H detected 1 H- 13 C HETCOR and 1 H- 15 N HETCOR 2D correlations measurements, in combination with 2D 1 H-1 H BaBa to characterize the loading process of naproxen/picolinamide and ibuprofen/nicotinamide co-crystals to SBA-15 and/or MCM-41 mesopores and their interactions.…”

Structural variety of heterosynthons in linezolid cocrystals with modified thermal properties

“…To overcome this limitation, the cocrystallization of a drug with a coformer from the generally regarded as safe (GRAS) list may be used (Food & Drug Administration, 2019), leading to a lower melting point of a crystal introduced into MSNs. Additional motivation and interest in modifying the thermal properties of pharmaceutical cocrystals and loading them into the pores of MSNs is associated with our previous observations that by changing the composition of cocrystals embedded into MSNs it is possible to control the release rate of an API (Skorupska et al, 2017). This can open new possibilities in therapeutic strategies.…”

The effects of pH, surfactant, ion concentration, coformer, and molecular arrangement on the solubility behavior of myricetin cocrystals

“…Pharmaceutical cocrystals are defined as a multi-component system that contains an active pharmaceutical ingredient (API) and cocrystal coformer (CCF) at a specific stoichiometric ratio that are linked via intermolecular interactions, such as hydrogen bonds, π – π packing, and van der Waals forces 1. , 2. , 3.…”

“…Pharmaceutical cocrystals are defined as a multi-component system that contains an active pharmaceutical ingredient (API) and cocrystal coformer (CCF) at a specific stoichiometric ratio that are linked via intermolecular interactions, such as hydrogen bonds, π – π packing, and van der Waals forces1., 2., 3.. As a promising formulation, pharmaceutical cocrystals can improve some of the physicochemical properties of APIs, such as the solubility, dissolution rate, bioavailability, and stability, without altering their inherent chemical structures4., 5..…”