Hydroxypropyl Cellulose for Drug Precipitation Inhibition: From the Potential of Molecular Interactions to Performance Considering Microrheology

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.

Purely Predicting the Pharmaceutical Solubility: What to Expect from PC-SAFT and COSMO-RS?

“…48,57,58 Further information and examples of the performance of COSMO-RS for API solubility can be found in refs 21,47,48,52,57,[59][60][61][62] . Other studies that demonstrate the usefulness of COSMO-based approaches in the pharmaceutical field (also beyond the solubility problem), can be found, e.g., in refs [63][64][65][66][67][68][69] .…”

“…COSMO-RS is considered a useful tool for qualitatively predicting API solubility and other phase equilibria and is reported to be an established solvent screening tool in the pharmaceutical industry. ,, Further information and examples of the performance of COSMO-RS for API solubility can be found in refs , , , , and , − . Other studies that demonstrate the usefulness of COSMO-based approaches in the pharmaceutical field (also beyond the solubility problem) can be found, for example, in refs − .…”