Spherical Agglomeration of Platy Crystals: Curious Case of Etodolac

• Published in: Crystal growth & design 2016-07, Vol.16 (7), p.4034-4042
• Main Authors: Jitkar, Supriya, Thipparaboina, Rajesh, Chavan, Rahul B, Shastri, Nalini R
• Format: Article
• Language: English
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.6b00563

The present study reports an intriguing case study of agglomeration of platy crystals into spheroids. Etodolac a nonsteroidal anti-inflammatory drug is mainly used for rheumatoid arthritis, with emerging applications in management of prostate cancer and Alzheimer’s disease. It is a BCS class II drug with poor flow and compressibility issues. Recrystallization using various solvents resulted in platy crystals. Different polymers like hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP), and copolymers poly­(ethylene glycol) (PEG 400), poly­(vinyl alcohol) (PVA), and Poloxamer were explored at various concentrations and in different combinations to provide systematic inputs for the development of spherical agglomerates with optimal sphericity, dissolution, yield, and mechanical properties suitable for direct compression. Effects of different process parameters on agglomeration were studied. Agglomerates obtained were characterized using SEM, DSC, and P-XRD and were evaluated for enhancements in flow, compressibility, and dissolution. All the agglomerates have shown improved flow properties and compressibility. Unlike plain drug, all spherical agglomerates have shown acceptable plastic behavior during compression studies resulting in tablets at low pressures. Agglomerates developed using a unique combination of HPMC, HPC, and PEG has shown 94% drug release in 15 min. The recrystallized spherical agglomerates can be used as readily compressible material for continuous manufacturing.