STUDIES ON PARACETAMOL CRYSTALS PRODUCED BY GROWTH IN AQUEOUS-SOLUTIONS

Paracetamol (P) crystals were grown from pure aqueous solutions containing varying concentrations (0.1-0.7% w/w of different additives. The additives were agar, gelatin, polyvinylpyrrolidone (PVP) and hydroxypropylmethyl cellulose (HPMC). The presence of the additives significantly modified the crystal habit from polygonal prismatic habit without additive, to rectangular/rod-shaped with gelatin, triangular/wing-shaped crystals with agar and rod-shaped/ellipsoidal/spherical crystals with PVP. The P crystal size and yield also decreased and were concentration (additive) dependent. However, PVP and HPMC showed a very high degree of crystal growth inhibition producing microcrystals with very low yield. The presence of additives also reduced the residual moisture content of P crystals, while gelatin improved the crystal flow rate. Stronger P crystals are produced with gelatin as indicated by the force at major fracture, whereas crystallization in agar solutions resulted in weaker crystals. P crystals produced from growth in aqueous solutions with and without the additives, agar or gelatin (0.1-0.7% w/w), were compressed into compacts. Crystallization of P improved its compressibility producing compacts without capping. The presence of additives in the growth medium increased the hardness and disintegration times of the compacts and these properties were also concentration dependent. Compacts of P crystals produced from the agar system had much longer disintegration times than those with gelatin as additive. Dissolution rates, as determined from the t(50) values, were in the order gelatin > no additive > agar.