Effect of Ultrasound on Crystallization of Paracetamol

Paracetamol, one of poorly water-soluble active pharmaceutical ingredients (APIs), has some shortcomings such as low dissolution rates and inefficient bioavailabilities when passed through oral of administration. In the present work, micronized paracetamol crystals were achieved by sonication on highly supersaturated solution. To attain highly supersaturated state of paracetamol solution, a nucleation inhibitor was used. To understand the effect of sonication, the measurements of induction time and the statistical approach on the induction time distribution were implemented by using a focused beam reflectance measurement probe (FBRM). Nucleation kinetics was evaluated in terms of supersaturation and nucleation rate was found to greatly increase by sonication. Using a thermodynamic model, the values of the effective interfacial energy for heterogeneous nucleation was estimated. Dissolution profile of produced paracetamol crystals was determined by an UV-visible spectrophotometer. It was found that micronized paracetamol crystals obtained in the present model have higher drug dissolution rates.