Compatibility of selected active pharmaceutical ingredients with poly(D, L-lactide-co-glycolide): Computational and experimental study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F22%3A43924994" target="_blank" >RIV/60461373:22340/22:43924994 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0939641122002089" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0939641122002089</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejpb.2022.09.013" target="_blank" >10.1016/j.ejpb.2022.09.013</a>
Alternative languages
Result language
angličtina
Original language name
Compatibility of selected active pharmaceutical ingredients with poly(D, L-lactide-co-glycolide): Computational and experimental study
Original language description
Biodegradable polyesters have emerged as a promising class of polymers for the development of efficient drug delivery systems for various treatments (including cancer treatment) due to their biocompatibility, low toxicity, and controlled drug release. This study presents a computational and experimental evaluation of the compati-bility of selected model active pharmaceutical ingredients (APIs) with poly(D, L-lactide-co-glycolide) (PLGA), which is a key parameter to designing drug delivery systems based on amorphous solid dispersions (ASDs) and polymeric micro-or nanoparticles. PLGA with different molar ratios of the monomer units, i.e., lactide to gly-colide ratio of 50:50 (PLGA50) or 75:25 (PLGA75), were investigated as polymeric carriers for the following model APIs: ibuprofen (IBU), paracetamol (PARA), naproxen (NAP), and indomethacin (IND). The phase dia-grams obtained by a combination of calorimetric measurements and modeling using the perturbed-chain sta-tistical associating fluid theory (PC-SAFT) equation of state (EOS) demonstrated low solubility of the model APIs in the studied copolymers at storage temperature (25 degrees C). The amorphous-amorphous phase separation was predicted by the PC-SAFT EOS for all API-PLGA systems and experimentally detected for the IBU-PLGA50, IBU-PLGA75, and NAP-PLGA75 systems. To investigate the physical stability of the API-PLGA systems and their link to the constructed phase diagrams, API-PLGA75 formulations were prepared using a melting process, and their solid-state properties were monitored over time. Of the analyzed API-PLGA75 formulations, only IND-PLGA75 remained in the amorphous state after 20 weeks of storage under dry conditions at 25 degrees C, while the other formulations recrystallized rapidly after preparation (IBU-PLGA75 and NAP-PLGA75) or after a limited storage period (PARA-PLGA75), reflecting poor compatibility of the investigated APIs with the PLGA copolymers and limited kinetic stabilization, as predicted from the constructed phase diagrams. Another important output of this work is the evaluation of the pure predictions of phase diagrams using the PC-SAFT EOS and its performance in ranking API-polymer compatibility.
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
<a href="/en/project/GA22-07164S" target="_blank" >GA22-07164S: Rational design of drug delivery systems based on tailored biodegradable polymers using an iterative in silico and experimental approach</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Pharmaceutics and Biopharmaceutics
ISSN
0939-6411
e-ISSN
1873-3441
Volume of the periodical
179
Issue of the periodical within the volume
říjen 2022
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
232-245
UT code for WoS article
000869794700001
EID of the result in the Scopus database
2-s2.0-85138798869