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Drug release from hydroxypropylcellulose gels cannot be statistically predicted from their viscometric and initial
David S Jones1, Gerard P Rafferty1, Gavin P Andrews1
1School of Pharmacy, Queen's University of Belfast, Belfast, Antrim, Northern Ireland, United Kingdom.
Carbohydrate Polymers
|January 23, 2021
Summary
Drug release from Hydroxypropylcellulose (HPC) platforms cannot be predicted by initial gel properties. This study found no correlation between rheological parameters and metronidazole release, indicating limitations for erosion-based drug delivery systems.
Area of Science:
- Materials Science
- Pharmaceutical Sciences
- Polymer Chemistry
Background:
- Hydroxypropylcellulose (HPC) is a widely used polymer in drug delivery systems.
- Understanding the relationship between polymer rheology and drug release kinetics is crucial for designing effective drug formulations.
- Previous studies have explored correlations between material properties and drug release, but a definitive link for HPC erosion-based systems remains unclear.
Purpose of the Study:
- To investigate the predictive power of rheological properties for metronidazole release from Hydroxypropylcellulose (HPC) platforms.
- To explore the influence of various solvents on the rheological characteristics of HPC solutions and gels.
- To establish relationships between viscometric and viscoelastic parameters and drug release kinetics.
Main Methods:
- Characterization of HPC solutions and gels in aqueous, alcoholic, and diol solvents using viscometry and oscillatory rheology.
- Drug release studies of metronidazole from HPC gels at pH 7.4 under sink conditions.
- Statistical modeling (multiple linear stepwise regression) to correlate rheological data with drug release profiles.
- Computational modeling (COSMO) to predict solvent-HPC interactions.
Main Results:
- Ethanol and water were identified as effective solvents for HPC, while diol solvents showed predicted higher interactions but lower intrinsic viscosities.
- HPC gels prepared with pentanediol or ethylene glycol exhibited the highest elasticity.
- No significant correlations were found between the rheological properties of dilute HPC solutions and the initial viscoelasticity of the gels.
- Drug release from HPC gels occurred through a combination of gel erosion and diffusion mechanisms.
- Crucially, no relationship was observed between the initial viscoelasticity of the HPC gels and the rate of metronidazole release.
Conclusions:
- Initial gel viscoelasticity and dilute solution properties of Hydroxypropylcellulose (HPC) do not reliably predict drug release kinetics.
- For HPC gel platforms that undergo erosion in aqueous environments, drug release cannot be forecasted based on pre-formulation rheological measurements.
- This finding highlights limitations in using rheological parameters as sole predictors for drug release in erosion-dominated delivery systems.