Simultaneously improving the mechanical properties, dissolution performance, and hygroscopicity of ibuprofen and flurbiprofen by cocrystallization with nicotinamide.

Shing Fung Chow, Miles Chen, Limin Shi, Albert H.L. Chow, Changquan Calvin Sun

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

To be fully exploitable in both formulation and manufacturing, a drug cocrystal needs to demonstrate simultaneous improvement of multiple key pharmaceutical properties over the pure drug crystal. The present work was aimed at investigating such feasibility with two model profen-nicotinamide cocrystals. Phase pure 1:1 ibuprofen-nicotinamide and flurbiprofen-nicotinamide cocrystals were prepared from solutions through rapid solvent removal using rotary evaporation,and characterized by DSC, PXRD, FTIR, phase solubility measurements, equilibrium moisture sorption analysis, dissolution testing and tabletability analysis. Temperature-composition phase diagrams constructed from DSC data for each profen and nicotinamide crystal revealed the characteristic melting point of the 1:1 cocrystal as well as the eutectic temperatures and compositions. Both cocrystals exhibited higher intrinsic dissolution rates than the corresponding profens. The cocrystals also sorbed less moisture and displayed considerably better tabletability than the individual profens and nicotinamide. Phase behaviors of 1:1 profen-nicotinamide cocrystal systems were delineated by constructing their temperature-composition phase diagrams. Cocrystallization with nicotinamide can simultaneously improve tableting behavior, hygroscopicity, and dissolution performance of ibuprofen and flurbiprofen. This could pave the way for further development of such cocrystal systems into consistent, stable, efficacious and readily manufacturable drug products.

Original languageEnglish (US)
Pages (from-to)1854-1865
Number of pages12
JournalPharmaceutical research
Volume29
Issue number7
DOIs
StatePublished - Jul 2012

Bibliographical note

Funding Information:
Financial support from the Chinese University of Hong Kong (research postgraduate studentship and conference travel grant for SFC) is gratefully acknowledged.

Fingerprint

Dive into the research topics of 'Simultaneously improving the mechanical properties, dissolution performance, and hygroscopicity of ibuprofen and flurbiprofen by cocrystallization with nicotinamide.'. Together they form a unique fingerprint.

Cite this