Physical characterization of drug:polymer dispersion behavior in polyethylene glycol 4000 solid dispersions using a suite of complementary analytical techniques.
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.
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Dipy M
DM
Vasa
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Namita
N
Dalal
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Jeffrey M
JM
Katz
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Rahul
R
Roopwani
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Akshata
A
Nevrekar
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Harshil
H
Patel
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Ira S
IS
Buckner
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282. Electronic address: wildfongp@duq.edu.
Peter L D
PLD
Wildfong
D007052:Ibuprofen / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
D004364:Pharmaceutical Preparations; D011108:Polymers; D011208:Powders; D011092:Polyethylene Glycols; D007052:Ibuprofen
crystallinity; miscibility; pair distribution function; physical characterization; polyethylene glycol (PEG); powder X-ray diffraction; solid dispersions; solubility; thermal analysis