Step-by-step standardization of the bottom-up semi-automated nanocrystallization of pharmaceuticals: a quality by design and design of experiments joint approach
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F24%3A00587261" target="_blank" >RIV/61389013:_____/24:00587261 - isvavai.cz</a>
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/smll.202306054" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/smll.202306054</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/smll.202306054" target="_blank" >10.1002/smll.202306054</a>
Alternative languages
Result language
angličtina
Original language name
Step-by-step standardization of the bottom-up semi-automated nanocrystallization of pharmaceuticals: a quality by design and design of experiments joint approach
Original language description
Nanosized drug crystals have been reported with enhanced apparent solubility, bioavailability, and therapeutic efficacy compared to microcrystal materials, which are not suitable for parenteral administration. However, nanocrystal design and development by bottom-up approaches are challenging, especially considering the non-standardized process parameters in the injection step. This work aims to present a systematic step-by-step approach through Quality-by-Design (QbD) and Design of Experiments (DoE) for synthesizing drug nanocrystals by a semi-automated nanoprecipitation method. Curcumin is used as a drug model due to its well-known poor water solubility (0.6 µg mL−1, 25 °C). Formal and informal risk assessment tools allow identifying the critical factors. A fractional factorial 24−1 screening design evaluates their impact on the average size and polydispersity of nanocrystals. The optimization of significant factors is done by a Central Composite Design. This response surface methodology supports the rational design of the nanocrystals, identifying and exploring the design space. The proposed joint approach leads to a reproducible, robust, and stable nanocrystalline preparation of 316 nm with a PdI of 0.217 in compliance with the quality profile. An orthogonal approach for particle size and polydispersity characterization allows discarding the formation of aggregates. Overall, the synergy between advanced data analysis and semi-automated standardized nanocrystallization of drugs is highlighted.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10404 - Polymer science
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Small
ISSN
1613-6810
e-ISSN
1613-6829
Volume of the periodical
20
Issue of the periodical within the volume
25
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
2306054
UT code for WoS article
001154290900001
EID of the result in the Scopus database
2-s2.0-85183933499