Hydroxypropyl Cellulose for Drug Precipitation Inhibition: From the Potential of Molecular Interactions to Performance Considering Microrheology
Type
01A - Beitrag in wissenschaftlicher Zeitschrift
Zusammenfassung
There has been recent interest in using hydroxypropyl cellulose (HPC) for supersaturating drug formulations. This study investigated the potential for molecular HPC interactions with the model drug celecoxib by integrating novel approaches in the field of drug supersaturation analysis. Following an initial polymer characterization study, quantum-chemical calculations and molecular dynamics simulations were complemented with results of inverse gas chromatography and broadband diffusing wave spectroscopy. HPC performance was studied regarding drug solubilization and kinetics of desupersaturation using different grades (i.e., HPC-UL, SSL, SL, and L). The results suggested that the potential contribution of dispersive interactions and hydrogen bonding depended strongly on the absence or presence of the aqueous phase. It was proposed that aggregation of HPC polymer chains provided a complex heterogeneity of molecular environments with more or less excluded water for drug interaction. In precipitation experiments at a low aqueous polymer concentration (i.e., 0.01%, w/w), grades L and SL appeared to sustain drug supersaturation better than SSL and UL. However, UL was particularly effective in drug solubilization at pH 6.8. Thus, a better understanding of drug–polymer interactions is important for formulation development, and polymer blends may be used to harness the combined advantages of individual polymer grades.
DOI der Originalausgabe
https://doi.org/10.1021/acs.molpharmaceut.1c00832Übergeordnetes Werk
Molecular Pharmaceutics
Jahrgang
19
Ausgabe
2
Seiten
690-703
Verlag / Hrsg. Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Washington