Crystallization of Polymorphic Sulfathiazole Controlled by Femtosecond Laser-Induced Cavitation Bubbles

Abstract

Crystals have been widely used in the pharmaceutical industry, structural elucidation, and other biomedical fields. Different polymorphs of one compound possess distinct physical and chemical properties. Some polymorphs are more favorable in applications such as drug delivery and structural characterization. However, owing to the complex mechanisms of the crystallization process, controlling the crystallization result is still difficult. In this study, we found that the femtosecond laser could be applied to control the crystallization of sulfathiazole. By introducing femtosecond laser irradiation, the crystal number and proportion of specific polymorphs were promoted. The interaction of the femtosecond laser with the solution was studied by time-resolved optical microscopy at a time scale of 200 fs to 50 μs. It is suggested that laser-induced cavitation bubbles act as nucleation centers in the crystallization process. Applying ultrasound to tune the bubble dynamics also has impact on the crystallization results. The control of the nucleation results was achieved through femtosecond laser-induced bubble generation. These results offer an approach for controlling the crystallization of sulfathiazole and also provide some knowledge on the process of laser-induced nucleation.

New Cocrystallization Method: Non-photochemical Laser-Induced Nucleation of a Cocrystal of Caffeine–Gallic Acid in Water

“…Compared to other organic compounds studied via NPLIN in the same experimental setup, the crystalline growth speed of the cocrystal is so far lower. For glycine, 15 carbamazepine, 29 and sulfathiazole, 34 the induction time is between 10 and 30 min and filtered after only 3 h, while the MZL limit varies from 1.5 to 7 days for glycine, 15 3 days for carbamazepine, 31 and 7 days for sulfathiazole. 34 In these three cases, MZL is lower than those observed with CAF-GAL cocrystals, crystallization kinetics is slower by a factor 10, and the size of the cocrystal is very small.…”

“…Cocrystals present different physicochemical properties than the pure API: solubility in water may be increased, stability can be enhanced, susceptibility to moisture can be reduced, and so forth. 28 Several APIs have been crystallized via NPLIN: L-histidine, 29 acetaminophen, 30 carbamazepine, 31 indomethacin, 32 sulfathiazole, 33,34 and aspirin. 35 However, no nucleation via NPLIN has been tried in the specific case of the cocrystals.…”

“…Several APIs have been crystallized via NPLIN: l -histidine, acetaminophen, carbamazepine, indomethacin, sulfathiazole, , and aspirin . However, no nucleation via NPLIN has been tried in the specific case of the cocrystals.…”

A review on laser-induced crystallization from solution

“…Also, it was observed that the length of the crystals decreased with an increase in the double pulse delay time. Finally, it was reported that the aspect ratio distribution Yu et al 97 demonstrated polymorph control of sulfathiazole in a mixture of water and ethanol supersaturated solution by focusing femtosecond laser light (800 nm) through a 5x objective for a period of 1 minute, 500 µm from the air-liquid interface, as shown in Figure 16i. In other experiments, the laser source was combined with ultrasound, using a 40 kHz, 50 W ultrasonic cleaning machine to check the influence of ultrasound exposure along with laserinduced nucleation.…”

Simultaneous control of polymorphism and morphology via gelatin induction for concomitant systems: case study of sulfathiazole

“…[14][15][16] Traditional thermodynamic and kinetic methods cannot achieve efficient polymorph separation. 17,18 Various external auxiliary methods such as supercritical CO 2 , 19 laser induction, 20,21 polymer induction, 22,23 self-assembled monolayers (SAMs), 24 gel phase crystallization, 25,26 etc. were applied to control the concomitant polymorphism.…”