Related Experiment Video
Updated: Jun 21, 2025
09:19
Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
Published on: March 16, 2020
7.0K
Screening, Synthesis, and Characterization of a More Rapidly Dissolving Celecoxib Crystal Form
Aaron O'Sullivan1,2, Enrico Spoletti2, Steven A Ross3
1SSPC Research Centre, University of Limerick, Limerick V94 T9PX, Ireland.
ACS Omega
|July 15, 2024
Summary
Scientists developed a new celecoxib (CEL) cocrystal with N-ethylacetamide (NEA) to improve drug solubility. This novel CEL·2NEA form shows over a twofold increase in dissolution rate compared to pure CEL.
Area of Science:
- Pharmaceutical Science
- Crystal Engineering
- Drug Delivery
Background:
- Poor solubility of active pharmaceutical ingredients (APIs) like celecoxib (CEL) hinders drug efficacy, leading to low concentrations and in vivo failure.
- Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) crucial for treating osteoarthritis and rheumatoid arthritis.
Purpose of the Study:
- To synthesize and characterize a novel cocrystal of celecoxib (CEL) to enhance its solubility and dissolution properties.
- To investigate the potential of cocrystallization as a strategy to overcome solubility limitations in APIs.
Main Methods:
- Computational screening of celecoxib (CEL) against generally recognized as safe (GRAS) coformers based on molecular complementarity and hydrogen bond propensity (HBP).
- Experimental screening of 17 potential coformers using liquid-assisted grinding (LAG), solvent evaporation (SE), gas antisolvent crystallization (GAS), and supercritical enhanced atomization (SEA).
- Characterization of the novel cocrystal form, celecoxib-di-N-ethylacetamide (CEL·2NEA), using single-crystal X-ray diffraction and desolvation studies.
Main Results:
- A new cocrystal, celecoxib-di-N-ethylacetamide (CEL·2NEA), was successfully isolated using N-ethylacetamide (NEA) as a liquid coformer.
- Single-crystal X-ray diffraction confirmed the crystal structure, revealing that both NEA molecules desolvate around 65 °C.
- The CEL·2NEA cocrystal demonstrated a significant improvement in dissolution rate, achieving more than a twofold increase compared to as-received CEL within 15 minutes.
Conclusions:
- The novel CEL·2NEA cocrystal effectively enhances the dissolution rate of celecoxib (CEL), addressing its poor solubility.
- Cocrystallization with N-ethylacetamide (NEA) presents a viable strategy for improving the pharmacokinetic profile of celecoxib (CEL).
- This study highlights the potential of rational cocrystal design to overcome API solubility challenges in pharmaceutical development.
