Ibuprofen in Mesopores of Mobil Crystalline Material 41 (MCM-41): A Deeper Understanding

Abstract

In this work, we compared two methods (incipient wetness and melting) for the encapsulation of ibuprofen in the pores of Mobil Crystalline Material 41 (MCM-41) through NMR (nuclear magnetic resonance) spectroscopy. (1)H NMR spectra were recorded under very fast MAS (sample spinning 60 kHz) conditions in both 1D and 2D mode (NOESY sequence). We also performed (13)C cross-polarization magic angle spinning (CP/MAS) experiments, (13)C single pulse experiments (SPE), and (1)H-(13)C HSQC HR/MAS (heteronuclear single quantum coherence high resolution) HR/MAS correlations. Evaluation of the encapsulation methods included an analysis of the filling factor of the drug into the pores. The stability of Ibu/MCM in an environment of ethanol or water vapor was tested. Our study showed that melting a mixture of Ibu and MCM is a much more efficient method of confining the drug in the pores compared to incipient wetness. The optimal experiments for the former method achieved a filling factor of approximately 60%. We concluded that the major limitation to the applicability of the incipient wetness method (filling factor ca. 20%) is the high affinity of solvent (typically ethanol) for MCM-41. We found that even ethanol vapor can remove Ibu from the pores. When a sample of Ibu/MCM was stored for a few hours in a closed vessel with ethanol vapor, Ibu was transported from the pores to the outer walls of MCM. We observed a similar phenomenon with water vapor, although this process is slower compared to the analogous procedure using ethanol. Our study clearly demonstrates that existing methods used to encapsulate drugs in mesoporous silica nanoparticles (MSNs) require reevaluation.

A Process for the Formation of Nanocrystals of Active Pharmaceutical Ingredients with Poor Aqueous Solubility in a Nanoporous Substrate

“…A recent NMR study on loading IBP in mesoporous silica (MCM-41, pore size 2.1−2.7 nm) has suggested that ethanol (hydroxyl groups) has a high affinity for the MCM-41 silica surface (hydrogen bonding with silanol groups) and so competes with IBP (carboxylic acid groups) when interacting with the silica material reducing its ability to load MCM-41 with a high content of IBP. 35 Hexane is a solvent incapable of forming hydrogen bonds and has a lower solubility for IBP relative to ethanol. We examined the effect of loading IBP within CPG using 2.5 mL of cold hexane as a rinse solvent where again 50% (w/v) IBP in iPrOH was used and the process run as standard.…”

“…35 We considered whether or not hydrogen bonding capability from the alcohol carrier solvents, interacting with silica surface, could limit the uptake of IBP within the nanopores of CPG, reducing the %w/w loading of IBP. DCM was chosen as a carrier solvent due its low viscosity and negligible hydrogen bonding capability (and therefore negligible interaction with silica surfaces) relative to the alcohols.…”

Implication of Water Molecules at the Silica–Ibuprofen Interface in Silica-Based Drug Delivery Systems Obtained through Incipient Wetness Impregnation

“…Moreover, we note that for BA@MCM actually two resonances at 5.1 and 4.7 ppm are observed, that are related to water molecules inside and outside the pores of the mesoporous silica. 27 These signals are much more intense than for Ibu@MCM that is an indication of the ease of water molecules to enter inside the mesopores which is higher for BA@MCM than for Ibu@MCM.…”

“…According to the literature, 27 2 H NMR spectroscopy is a pertinent tool to study dynamics of solids and encapsulated molecules in particular. 40 We recorded variable temperature 2 H static NMR experiments to explore the dynamical behavior of encapsulated benzoic acid (BA-D5@MCM) and compared …”

“…22 Recent literature showed that drugs confined in porous matrices are submitted to a confinement effect that influences their physical state at room temperature 23,24,25,26,27 . It is generally admitted that the exacerbated mobility evidenced in the case of encapsulated ibuprofen influences strongly the release profile observed in vitro.…”