Physical Characterization of Drug:Polymer Dispersion Behavior in Polyethylene Glycol 4000 Solid Dispersions using a Suite of Complementary Analytical Techniques

Abstract

Fifteen model drugs were quenched from 3:1 (w/w) mixtures with polyethylene glycol 4000 (PEG4000). The resulting solids were characterized using powder X-ray diffraction (PXRD), analysis of pair distribution function-transformed PXRD data (where appropriate), hot-stage polarized light microscopy, and differential scanning calorimetry (DSC). Drug/polymer dispersion behavior was classified using the data from each technique, independent of the others, and limitations to single-method characterization of PEG-based systems are highlighted. The data from all characterization techniques were collectively used to classify dispersion behavior, which was compared with single-technique characterization. Of the 15 combinations, only six resulted in solids whose dispersion behavior was consistently described using each standalone technique. The other nine were misclassified using at least one standalone technique, mainly because the phase behavior was ambiguously interpreted when only the data from one technique were considered. The data indicated that a suite of complementary techniques provided better classifications of the phase behavior. Of all the quenched solids, only cimetidine was fully dispersed in PEG4000, suggesting that it solidified from a completely miscible mixture of molten drug and polymer that did not phase separate upon cooling. In contrast, ibuprofen and PEG4000 completely recrystallized during preparation, whereas the remaining 13 drugs were partially dispersed in PEG4000 at this composition.

Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs

“…However, thermal analysis revealed partial miscibility and it was concluded that the drug has limited miscibility in polymer. 72 Poloxamer 188 (Lutrol ® F 127) (MW:~10000-14000, T m~5 5 C)…”

Modeling and Prediction of Drug Dispersability in Polyvinylpyrrolidone-Vinyl Acetate Copolymer Using a Molecular Descriptor

“…Previous work has demonstrated the necessity of using multiple complementary characterization techniques to appropriately classify phase behavior of amorphous solid dispersions. [10][11][12] When used independently, the inherent limitations of each method can lead to erroneous inferences regarding the true state of the system. 13 In the present work, a combination of techniques including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), polarized light and hot stage microscopy, and pair distribution function (PDF) analysis of PXRD data were collectively used for these experiments, to improve the certainty of dispersability classifications.…”

“…The use of this particular suite of analytical techniques to accurately categorize solid dispersion behavior was discussed in detail in a previous publication. 10 Powder X-Ray Diffraction PXRD patterns were generated consistent with previous work with these systems, to allow comparison. 9 Diffraction data were collected using an X'Pert Pro MPD system (PANalytical B.V., Almelo, the Netherlands) in transmission mode, equipped with a Cu anode (l ¼ 1.5406 Å), elliptical mirror, and X'Celerator™ detector.…”

Crystallization Kinetics of Indomethacin/Polyethylene Glycol Dispersions Containing High Drug Loadings

“…The intensity of the unique diffraction peak of PEG at19.2° appeared to be inversely proportional to the final temperature. This peak decreased in intensity when the temperature increased, suggesting lower crystallinity of PEG when cooled to higher temperature.…”