Sonocrystallization—Case Studies of Salicylamide Particle Size Reduction and Isoniazid Derivative Synthesis and Crystallization

Abstract

Two case studies of salicylamide particle size reduction and isoniazid derivative synthesis and crystallization realized using sonocrystallization were investigated. The size, habit, structure, thermal behavior, and spectrometric properties of sonocrystallized crystals were analyzed through scanning electron microscopy (SEM), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. The effects of the operating parameters, such as sonication intensity, sonication duration, and solution concentration, on sonocrystallization were compared. The crystal size of salicylamide was reduced from 595 µm (the original size) and was efficiently manipulated to be between 40 and 80 µm. Moreover, compared with the crystal habits of unprocessed crystals and recrystallized crystals fabricated through conventional methods, the crystal habit of salicylamide could be modified to present a regular shape. The structure, thermal behavior, and spectrometric properties of sonocrystallized salicylamide were found to be in agreement with those of an unprocessed sample. For producing isoniazid derivative crystals, N-(propan-2-ylidene)-isonicotinohydrazide was synthesized using isoniazid in acetone at 318 K. The resulting solution was then cooled by applying power ultrasound to isolate N-(propan-2-ylidene)-isonicotinohydrazide crystals. The solid-state properties of the synthesized N-(propan-2-ylidene)-isonicotinohydrazide was verified through PXRD, DSC, and FTIR spectroscopy. The feasibility of particle size manipulation was then demonstrated through sonocrystallization.

Comparative Study of Different Crystallization Methods in the Case of Cilostazol Crystal Habit Optimization

“…It can reduce the metastable zone width, and generate rapid, uniform mixing, which reduces the agglomeration of particles [18,19]. Higher sonication intensity and longer sonication time favour the formation of smaller crystals with narrow PSD [20][21][22].Impinging jet crystallization is a relatively new field for the researchers in pharmaceutical manufacturing and industrial crystallization [23]. However, it is proved that this method effectively reduces particle size, as well as it has the potential advantage to produce reproducible products with small average particle size and narrow PSD [24].…”

“…It can reduce the metastable zone width, and generate rapid, uniform mixing, which reduces the agglomeration of particles [18,19]. Higher sonication intensity and longer sonication time favour the formation of smaller crystals with narrow PSD [20][21][22].…”

Particle Size and Crystal Habit Modification of Active Pharmaceutical Ingredient Using Cooling Sonocrystallization: A Case Study of Probenecid

“…Similar trend was also observed in our previous case study for sonocrystallization of salicylamide. [ 26 ]…”

“…[ 16‐18 ] With the emerging of sonocrystallization in practical use, several case studies have been reported in the literature in recent years for recrystallization of biological compounds such as aspirin, l ‐arginine hydrochloride, ferulic acid, cinnamic acid, oxalic acid, l ‐phenylalanine, salicylamide, isoniazid derivative, telmisartan, lactose, lysozyme, and l ‐glutamic acid. [ 19‐30 ]…”