Journal article
The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations
Journal of pharmaceutical sciences, Vol.114(1), pp.289-303
01/2025
DOI: 10.1016/j.xphs.2024.09.020
PMID: 39349295
Abstract
One of the limitations with an amorphous solid dispersion (ASD) formulation strategy is low drug loading. Hydrophobic drugs have poor wettability and require a substantial amount of polymer to stabilize the amorphous drug and facilitate release. Using grazoprevir and hypromellose acetate succinate as model drug and polymer respectively, the interplay between particle surface composition, particle wettability, and release performance was investigated. A hierarchical particle approach was used where the surfaces of high drug loading ASDs generated by either solvent evaporation or co-precipitation were further modified with a secondary excipient (i.e., polymer or wetting agent). The surface-modified particles were characterized for drug release, wettability, morphology, and surface composition using two-stage dissolution studies, contact angle measurements, scanning electron microscopy, and X-ray photoelectron spectroscopy, respectively. Despite surface modification with hydrophilic polymers, hierarchical cPAD particles did not consistently exhibit good release performance. Contact angle measurements showed that the secondary excipient had a profound impact on particle wettability. Particles with good wettability showed improved drug release relative to particles that did not wet well, even with similar drug loadings. These observations underscore the intricate interplay between particle wettability and performance in amorphous dispersion formulations and illustrate a promising hierarchical particle approach to formulate high drug loading amorphous dispersions with improved dissolution performance.
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Details
- Title: Subtitle
- The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations
- Creators
- Tze Ning Hiew - Purdue University West LafayetteMarina A. Solomos - MSDPrapti Kafle - MSDHector Polyzois - Purdue University West LafayetteDmitry Y. Zemlyanov - Purdue University West LafayetteAshish Punia - MSDDaniel Smith - MSDLuke Schenck - MSDLynne S. Taylor - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.114(1), pp.289-303
- DOI
- 10.1016/j.xphs.2024.09.020
- PMID
- 39349295
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- Elsevier Inc
- Grant note
- Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
The authors gratefully acknowledge Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for funding this study.
- Language
- English
- Electronic publication date
- 09/28/2024
- Date published
- 01/2025
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984721139902771
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