Evaluation on the Drug–Polymer Mixing Status in Amorphous Solid Dispersions at the Early Stage Formulation and Process Development

Classical Least Squares Combined with Spectral Interval Selection Using Genetic Algorithm for Prediction of Constituents in Pharmaceutical Solid Dosage Forms from near Infrared Chemical Imaging Data

“…The characterisation of pharmaceutical solid dosage forms (SDFs) using near infrared spectroscopy coupled with chemical imaging (NIR-CI) is extended to a wide range of applications related to quality control of end-products, e.g. active pharmaceutical ingredients (APIs) and excipient blending, [1][2][3][4][5][6][7] polymorphism, 8,9 counterfeit identification 10,11 and coatings. 12 NIR-CI and other hyperspectral imaging techniques based on vibration spectroscopy, like mid-IR, Raman and terahertz, are relevant due to the fast and non-invasive extraction of chemical information about the distribution of constituents in solid samples.…”

Structural Characterization of Amorphous Solid Dispersions

“…Local distribution of nuclear spin density Spatial mapping of the associated component (API, polymer or dissolution medium) using T (Bikiaris et al 2005;De Zordi et al 2012;Karavas et al 2007a, b;Ma et al 2013;Nakayama et al 2009) Ultimate spatial resolution for analyzing compositional heterogeneities, density variations, grain boundaries, etc. Reasonable contrast provided by hetero-elemental API for the measurement of the dimension of amorphous drug nano-clusters dispersed in the polymer matrix TEM/EDS for drug-polymer miscibility, i.e., molecularly mixed systems appear as a continuous matrix without elemental localization (lack of local elemental spikes) Spatial distinction of nanoscopic physical structure among amorphous, crystalline, and other mesophases in heterogeneous polymeric dispersion using selective negative staining of unsaturated API by heavy metal oxides (e.g., (Lauer et al 2011Meeus et al 2013;Qi et al 2013a, b) (Antal et al 2013;Bölcskei et al 2011;Chieng et al 2013a, b;Gottnek et al 2013;Szabó et al 2011;Szente et al 2009;Zelkóa et al 2006) Very Study of miscibility in product with low drug content (0.5-1 %w/w) Estimation of domain size and identification of molecular cluster to dispersion possible Selective Not applicable for high drugloading system as API molecular proximity below FRET distance Fluorescent properties required and FRET should occur Neutron scattering (Bordallo et al 2012;Lerbret et al 2012;Magazù et al 2008;Magazù et al 2010;Qi et al 2013a, b) Molecular dynamics and structural relaxation of multicomponent amorphous systems Small-angle neutron scattering for polymer-surfactant interaction during dissolution of ternary ASD Sample preparation tedious Requires isotope labeling or enrichment ASD amorphou...…”