Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions

Abstract

Based on the observed ability of mid-IR analysis to enable the characterization of intermolecular polyphenol-polymer interactions and based on the correlation between the extent of intermolecular interactions and the crystallization-inhibiting performance of polymers, it can be concluded that this technique is an important tool for the rational formulation of solid dispersions with optimized physical stability.

Application of Vibrational Spectroscopy to Study Solid-state Transformations of Pharmaceuticals

“…Again, the two bands at 2820 and 2770 cm -1 of the dimethylamino group of Eudragit disappeared in E100 ASDs confirming the presence of ionic interactions that stabilize the amorphous form as in the case of resveratrol, while H bonding is limited or weak. Using quercetin and naringenin as model compounds, Taylor's group confirmed that the analysis of the relative strength of ionic and H bonding interactions by mid-IR spectroscopy presents an efficient tool for predicting the ability of a polymer to prevent recrystallization of a given API [13]. Similar results were obtained in a study on felopidine ASDs in which an inverse correlation between the strength and extent of H bonding between API and polymer (as judged from the IR data) and crystal growth was established [214].…”

“…The availability of accurate quantification methods is essential for understanding the transformation kinetics of an API and thus for assessing the stability range of a given solid-state form. Vibrational spectroscopies probe intermolecular interactions and are therefore studied as potential tools for predicting the stability of solid-state formulations [13]. Moreover, NIR and Raman spectroscopy which can be easily coupled to fiber-optic probes, are also ideally suited as process analytical technology (PAT) tools.…”

Amorphous Solid Dispersions

“…Monitoring amorphous-tocrystalline transition as a function of temperature and/or time Brittle ASD with higher drug content inappropriate for DMA analysis Activation energy for α,β process between that measured by DRS and TSC T g measured higher than calorimetric T g ASD compact preparation may risk the alteration of the physical structure Composition-dependent hardness, reduced, and storage moduli obtained by nano-DMA provide miscibility data Table 14.5 Vibrational spectroscopic and microscopic analysis of ASD structure and possible hurdles Miscibility and molecular interactions (Andrews et al 2010;Breitkreitz and Poppi 2012;Hédoux et al 2011;Padilla et al 2010;Rumondor et al 2011;Wegiel et al 2012;Zeitler et al 2007) Crystallinty/crystallization (Chan et al 2004;Hédoux et al 2011;Hédoux et al 2009;Kao et al 2012;Palermo et al 2012a, b;Priemel et al 2012;Sinclair et al 2011;Vehring et al 2012) Interference/limitations (Gendrin et al 2008;Jørgensen et al 2009;Matero et al 2013;Taylor et al 2001...…”

“…Homo-(drug-drug, polymer-polymer) versus heteromolecular (drug-polymer) interactions, conformational states, dipolar self-and interassociation, phase-separation Raman signals are less affected by water peaks but confronted by fluorescence related artifacts from elastic scattering Table 14.5 (continued) Miscibility and molecular interactions (Andrews et al 2010;Breitkreitz and Poppi 2012;Hédoux et al 2011;Padilla et al 2010;Rumondor et al 2011;Wegiel et al 2012;Zeitler et al 2007) Crystallinty/crystallization (Chan et al 2004;Hédoux et al 2011;Hédoux et al 2009;Kao et al 2012;Palermo et al 2012a, b;Priemel et al 2012;Sinclair et al 2011;Vehring et al 2012) Interference/limitations (Gendrin et al 2008;Jørgensen et al 2009;Matero et al 2013;Taylor et al 2001) Vibrational (MIR, NIR, Raman, THz) microscopy (imaging/mapping) serves for fast and unambiguous quantification of the different solid forms of API in matrix, high signal-to-noise ratio and spatiochemical resolution Physical states and d...…”

The effects of polymer carrier, hot melt extrusion process and downstream processing parameters on the moisture sorption properties of amorphous solid dispersions

“…To investigate the moisture-induced changes in the solid dispersion, utilizing Fourier transform infrared (FTIR) spectroscopy in the analysis provides several advantages. [23] Sensitive and non-invasive characterization of drugpolymer interactions can be performed quickly, even with the controlled sample temperature and atmosphere. Moreover, FTIR chemical imaging provides straightforward information of miscibility or mixing of the drug and polymer.…”