Increase in Solubility of Poorly-Ionizable Pharmaceuticals by Salt Formation: A Case of Agomelatine Sulfonates
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00480929" target="_blank" >RIV/61388963:_____/17:00480929 - isvavai.cz</a>
Alternative codes found
RIV/60461373:22310/17:43914798 RIV/60461373:22340/17:43914798 RIV/00216208:11320/17:10370291
Result on the web
<a href="http://dx.doi.org/10.1021/acs.cgd.7b00805" target="_blank" >http://dx.doi.org/10.1021/acs.cgd.7b00805</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.cgd.7b00805" target="_blank" >10.1021/acs.cgd.7b00805</a>
Alternative languages
Result language
angličtina
Original language name
Increase in Solubility of Poorly-Ionizable Pharmaceuticals by Salt Formation: A Case of Agomelatine Sulfonates
Original language description
The search for new solid forms of an active pharmaceutical ingredient (API) is an important step in drug development. Often, an API has a low water solubility, which then leads to low oral bioavailability. For basic or acidic APIs, the rational solution is the preparation of salts. For neutral, poorly ionizable, compounds, the cocrystallization is often the only choice. Agomelatine, a poorly soluble ”nonionizable” amide acting as a melatonergic antidepressant is a typical representative of such class of compounds. Until recently, the only multicomponent forms of agomelatine were cocrystals. In this work, we report the preparation of three salts of agomelatine (hydrogensulfate, mesylate, and besylate) and their solvated forms, along with their crystallographic characterization. Interestingly, the crystal structures of the solvated and nonsolvated hydrogensulfates were determined from the same crystal via a topotactic transformation. In all of the structures, the agomelatine molecule was positively charged with the amide oxygen being protonated. The salt formation was also confirmed by solid state nuclear magnetic resonance measurements and density functional theory calculations. By sulfonate salt formation, up to similar to 200-times faster dissolution of agomelatine was achieved, which proves that salts might be an attractive alternative even for the poorly ionizable compounds.
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
10403 - Physical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Crystal Growth & Design
ISSN
1528-7483
e-ISSN
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Volume of the periodical
17
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
5283-5294
UT code for WoS article
000412718100035
EID of the result in the Scopus database
2-s2.0-85042508930