Stabilization of Metastable Indomethacin α in Cellulose Nanocrystal Aerogel Scaffolds
1
School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
2
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Il Won Kim
Pharmaceutics 2021, 13(4), 441; https://doi.org/10.3390/pharmaceutics13040441
Received: 27 February 2021
/
Revised: 19 March 2021
/
Accepted: 22 March 2021
/
Published: 24 March 2021
(This article belongs to the Special Issue Controlled Crystallization of Active Pharmaceutical Ingredients)
Indomethacin (IM) is a small molecule active pharmaceutical ingredient (API) that exhibits polymorphism with the γ-form being the most thermodynamically stable form of the drug. The α-form is metastable, but it exhibits higher solubility, making it a more attractive form for drug delivery. As with other metastable polymorphs, α-IM undergoes interconversion to the stable form when subjected to certain stimuli, such as solvent, heat, pH, or exposure to seed crystals of the stable form. In this study, IM was crystallized into cellulose nanocrystal aerogel scaffolds as a mixture of the two polymorphic forms, α-IM and γ-IM. Differential scanning calorimetry (DSC) and Raman spectroscopy were used to quantitatively determine the amount of each form. Our investigation found that the metastable α-IM could be stabilized within the aerogel without phase transformation, even in the presence of external stimuli, including heat and γ-IM seed crystals. Because interconversion is often a concern during production of metastable forms of APIs, this approach has important implications in being able to produce and stabilize metastable drug forms. While IM was used as a model drug in this study, this approach could be expanded to additional drugs and provide access to other metastable API forms.
View Full-Text
Keywords:
crystallization; indomethacin; cellulose nanocrystal; aerogel; polymorphism; Raman spectroscopy; metastability; polymorph stabilization
▼
Show Figures
Graphical abstract
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
PDF-Document (PDF, 321 KiB)
MDPI and ACS Style
Banerjee, M.; Brettmann, B. Stabilization of Metastable Indomethacin α in Cellulose Nanocrystal Aerogel Scaffolds. Pharmaceutics 2021, 13, 441. https://doi.org/10.3390/pharmaceutics13040441
AMA Style
Banerjee M, Brettmann B. Stabilization of Metastable Indomethacin α in Cellulose Nanocrystal Aerogel Scaffolds. Pharmaceutics. 2021; 13(4):441. https://doi.org/10.3390/pharmaceutics13040441
Chicago/Turabian StyleBanerjee, Manali, and Blair Brettmann. 2021. "Stabilization of Metastable Indomethacin α in Cellulose Nanocrystal Aerogel Scaffolds" Pharmaceutics 13, no. 4: 441. https://doi.org/10.3390/pharmaceutics13040441
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
