CORRELATION BETWEEN PHYSICOCHEMICAL PROPERTIES AND COHESIVE BEHAVIOR OF FUROSEMIDE CRYSTAL MODIFICATIONS

This study reports the influence of changes in crystal form, with subs equent changes in physico-chemical properties, on the cohesive propert ies of furosemide powders. Two known polymorphs and three crystal habi ts were prepared by changing the crystallisation solvent and velocity. Crystallised products were characterised by their XRD profiles. Powde r properties including solid-state photochemical reactivity, particle size and distribution, density, wettability and dissolution were measu red. Fine particles of form I, mean size 3 mu m, were extremely cohesi ve, mean size of agglomerates 108 mu m, and poorly wettable, contact a ngle > 90 degrees. Changes in the crystal habit of form I led to the c rystallisation of large (mean size > 50 mu m) tabular and rod shape, l ess cohesive but also poorly wettable (contact angle > 90 degrees) par ticles. These large particles although not cohesive had poor dissoluti on properties. Milled particles with a mean size of smaller than 10 mu m, obtained from the large crystals were again cohesive. The method o f preparation of form II produced small plate like crystals, mean size 8 mu m, fractionally more wettable, contact angle 75 degrees, and not as cohesive, mean size agglomerates 25 mu m. Milling to a mean size o f 4 mu m increased the cohesive properties because the mean size of ag glomerates was then 53 mu m. Different crystal habits of form I did no t show a difference in degradation during the nucleation period, mean rate constant 1.4x10(-2) h(-1) and the growth period, mean rate consta nt 2.4x10(-2) h(-1). In summary crystal modification improved the wett ability and cohesive properties of furosemide particles without changi ng the solid-state stability of the drug. The dissolution properties o f larger less cohesive particles were however poor and milling, to inc rease the surface area available for dissolution, increased the cohesi ve properties of particles.