Effects of initial concentration and seeding procedure on crystallisation of orthorhombic paracetamol from ethanolic...

The effects of some crystallisation conditions on the formation of orthorhombic paracetamol from ethanolic solution are examined when seeding technique is applied under fixed agitation (700 rpm) and harvesting time (30 min). Three equally spaced levels were used for initial concentration, C(I) (30 +/- 4% w/v), for seeding temperature, T(S) (7 +/- 7 degrees C) and for cooling temperature, T(C) (-10 +/- 10 degrees C). The influences on parameters of temperature change in the crystallisation solution were quantitatively determined as were influences on crystal yield (Y%), crystal size and shape, and orthorhombic content of the final crystalline product. Conditions for improvement of Y% under reproducible formation of orthorhombic form were elucidated. It was found that Y% increases remarkably by increasing C(I) but there is a corresponding decrease in the content of orthorhombic form. Increased content of monoclinic form is explained by nucleation under conditions of high C(I) (34% w/v), low seeding temperature (below 7 degrees C) and long seeding time (more than 14.7 min) in addition to transformation of grown orthorhombic seeds. However, reproducible formation of pure orthorhombic form is possible at medium C(I) (30% w/v) and optimal crystal yield (60.9% w/w) corresponds to -20 degrees C T(C) and 0 degrees C seeding temperature. Crystal size is affected by all the crystallisation conditions due to the alteration in the degree of supersaturation, and consequently, in the nucleation and growth processes. Aspect ratio is affected due to the presence of less elongated monoclinic crystals. The fullness ratio increases with the cooling temperature but decreases with the initial concentration, probably because of secondary nucleation on the crystal surfaces or erosion due to initiation of transformation.