Simultaneously Improving the Mechanical Properties, Dissolution Performance, and Hygroscopicity of Ibuprofen and Flurbiprofen by Cocrystallization with Nicotinamide

• Published in: Pharmaceutical research 2012-07, Vol.29 (7), p.1854-1865
• Main Authors: Chow, Shing Fung, Chen, Miles, Shi, Limin, Chow, Albert H. L., Sun, Changquan Calvin
• Format: Article
• Language: English
• Subjects: Analgesics - chemistry; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Calorimetry, Differential Scanning; Crystallization; Crystallization - methods; Flurbiprofen - chemistry; General pharmacology; Ibuprofen - chemistry; Mechanical properties; Medical Law; Medical sciences; Models, Molecular; Niacinamide - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Phase transitions; Powder Diffraction; Research Paper; Solubility; Spectroscopy, Fourier Transform Infrared; Tablets; Vitamin B Complex - chemistry; Wettability; X-Ray Diffraction
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-012-0709-5

ABSTRACT Purpose 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. Methods 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. Results 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. Conclusions 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.