Hydroxypropyl Cellulose for Drug Precipitation Inhibition: From the Potential of Molecular Interactions to Performance Considering Microrheology
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Authors
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Publication date
10.01.2022
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01A - Journal article
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Parent work
Molecular Pharmaceutics
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Volume
19
Issue / Number
2
Pages / Duration
690-703
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Publisher / Publishing institution
American Chemical Society
Place of publication / Event location
Washington
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Abstract
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.
Keywords
bioenabling formulation, solid dispersion, supersaturation, precipitation inhibition, hydroxypropyl cellulose, molecular dynamics simulation, microrheology
Subject (DDC)
500 - Naturwissenschaften
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ISBN
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1543-8384
1543-8392
1543-8392
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
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Peer review of the complete publication
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Closed
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Citation
STOYANOV, Edmont, Andreas NIEDERQUELL und Martin KUENTZ, 2022. Hydroxypropyl Cellulose for Drug Precipitation Inhibition: From the Potential of Molecular Interactions to Performance Considering Microrheology. Molecular Pharmaceutics. 10 Januar 2022. Bd. 19, Nr. 2, S. 690–703. DOI 10.1021/acs.molpharmaceut.1c00832. Verfügbar unter: https://doi.org/10.1021/acs.molpharmaceut.1c00832