|Abstract:||Acoustic cavitation occurs when ultrasound is applied to a liquid. Bubbles are generated, oscillate, expand and, when specific criteria are met, implosively collapse. These collapses generate hot spots and shockwaves. Hot spots have intense local temperatures (~5,000 K) and pressures (~1,000 atm), and a rapid heating and cooling rate (> 1010 K s-1). Shockwaves can induce crystallization, i.e., sonocrystallization, or break existing crystals, i.e., sonofragmentation in solid-liquid mixtures.
The sonofragmentation of ionic and molecular crystals is discussed in Chapters 2 and 3. When ultrasound was applied to slurries of ionic or molecular crystals, crystal breakage occurred not by interparticle collision but by direct interactions between crystals and shockwaves.
Sonofragmentation rates depended strongly on the strength of the crystal material, as described by its Vickers hardness or Young’s modulus. This is a mechanochemical extension of the Bell–Evans–Polanyi Principle or Hammond’s Postulate: i.e., activation energies for solid fracture correlate with the binding energies of solids. In addition, from comparisons of sonofragmentation patterns between ionic and molecular crystals, it was confirmed that the sonofragmentation of ionic crystals was more sensitive to changes in material hardness than that of molecular crystals. Finally, two possible mechanisms of particle breakage via sonofragmentation were suggested: particle breakage from defects formed by shock-induced compression-expansion of the initial crystal and particle breakage from defects created during shock-induced bending or torsion of the initial crystal.
In Chapters 4 and 5, the sonocrystallization of pharmaceutical agents having inherently low water solubility is discussed. Chapter 4 describes the development of a spray sonocrystallization system. Spray sonocrystallization produced nano-scale carboxyphenyl salicylate crystals (c.a. 100 nm) with a narrow size distribution. The crystal size was controllable by changing the initial solute concentration. In Chapter 5, carbamazepine crystals were produced via various crystallization methods, including spray sonocrystallization. Crystal sizes, solubility and dissolution rates were compared among carbamazepine crystals generated by five different crystallization methods. Spray sonocrystallization produced the smallest crystals and resulted in the most rapid observed dissolution rate in water.