Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F20%3A43921126" target="_blank" >RIV/60461373:22340/20:43921126 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.mdpi.com/1999-4923/12/8/741" target="_blank" >https://www.mdpi.com/1999-4923/12/8/741</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/pharmaceutics12080741" target="_blank" >10.3390/pharmaceutics12080741</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
Popis výsledku v původním jazyce
The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR-TER cocrystal formation was ball milling. The stoichiometry of the ITR-TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR-TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR-oxalic acid > ITR-succinic acid > ITR-TER. Additionally, the ITR-TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations.
Název v anglickém jazyce
Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
Popis výsledku anglicky
The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR-TER cocrystal formation was ball milling. The stoichiometry of the ITR-TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR-TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR-oxalic acid > ITR-succinic acid > ITR-TER. Additionally, the ITR-TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
20401 - Chemical engineering (plants, products)
Návaznosti výsledku
Projekt
—
Návaznosti
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
PHARMACEUTICS
ISSN
1999-4923
e-ISSN
—
Svazek periodika
12
Číslo periodika v rámci svazku
8
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
18
Strana od-do
—
Kód UT WoS článku
000564051000001
EID výsledku v databázi Scopus
2-s2.0-85090398118