Formation of the first non-isostructural cocrystal of apremilast explained

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F20%3A43921233" target="_blank" >RIV/60461373:22340/20:43921233 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378271:_____/20:00540593

Výsledek na webu

<a href="https://pubs.acs.org/doi/abs/10.1021/acs.cgd.0c00393" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acs.cgd.0c00393</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.cgd.0c00393" target="_blank" >10.1021/acs.cgd.0c00393</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Formation of the first non-isostructural cocrystal of apremilast explained

Popis výsledku v původním jazyce

Search for new multicomponent solid forms has become a key step in pharmaceutical drug development. Apremilast, a poorly soluble API used for the treatment of psoriatic arthritis, was used as a model compound in this work. There have been several isostructural cocrystals of this API already described in the literature. In this paper, a new isostructural cocrystal (with phthalic acid) and solvates (with o-xylene and fluorobenzene) of the studied compound were successfully designed. Furthermore, to the best of our knowledge, this work is the first ever to prepare a non-isostructural cocrystal of apremilast with cinnamic acid. The crystal structures of all the new multicomponent forms were successfully solved using single crystal X-ray diffraction. The differences between the formation of the isostructural and non-isostructural forms are explained in detail using the structural characterization of the prepared forms and the density functional theory calculations (B3LYP/6-31G(d,p) level of theory). The physicochemical characterization complemented the structural one, including the thermal properties (differential scanning calorimetry, DSC) and the intrinsic dissolution rate (IDR). The samples were further characterized by X-ray powder diffraction (XRPD) and Raman spectroscopy. The dissolution experiments showed that the new multicomponent solids can improve the intrinsic dissolution rate by up to 500% compared to the polymorph of apremilast used in the marketed drug product. Copyright © 2020 American Chemical Society.

Název v anglickém jazyce

Formation of the first non-isostructural cocrystal of apremilast explained

Popis výsledku anglicky

Search for new multicomponent solid forms has become a key step in pharmaceutical drug development. Apremilast, a poorly soluble API used for the treatment of psoriatic arthritis, was used as a model compound in this work. There have been several isostructural cocrystals of this API already described in the literature. In this paper, a new isostructural cocrystal (with phthalic acid) and solvates (with o-xylene and fluorobenzene) of the studied compound were successfully designed. Furthermore, to the best of our knowledge, this work is the first ever to prepare a non-isostructural cocrystal of apremilast with cinnamic acid. The crystal structures of all the new multicomponent forms were successfully solved using single crystal X-ray diffraction. The differences between the formation of the isostructural and non-isostructural forms are explained in detail using the structural characterization of the prepared forms and the density functional theory calculations (B3LYP/6-31G(d,p) level of theory). The physicochemical characterization complemented the structural one, including the thermal properties (differential scanning calorimetry, DSC) and the intrinsic dissolution rate (IDR). The samples were further characterized by X-ray powder diffraction (XRPD) and Raman spectroscopy. The dissolution experiments showed that the new multicomponent solids can improve the intrinsic dissolution rate by up to 500% compared to the polymorph of apremilast used in the marketed drug product. Copyright © 2020 American Chemical Society.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20401 - Chemical engineering (plants, products)

Projekt

<a href="/cs/project/TJ02000256" target="_blank" >TJ02000256: Zlepšování vlastností léčiv pomocí pokročilých multikomponentních forem léčivých látek</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Crystal Growth &amp; Design

ISSN

1528-7483

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

5785-5795

Kód UT WoS článku

000569269800019

EID výsledku v databázi Scopus

2-s2.0-85092252580