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Anti-solvent sonocrystallization for nano-range particle size of telmisartan through Taguchi and Box–Behnken design

Chetan Sharma, Meghal A. Desai, and Sanjaykumar R. Patel

Sardar Vallabhbhai National Institute of Technology, Surat, India



Abstract: This study investigates the effect of process parameters [like solvent to anti-solvent ratio (1:2–1:4), injection rate (1–10 mL/min), drug concentration (5–15 mg/mL), crystallization temperature (20–30 °C), sonication amplitude (20–60%), and sonication time (2–15 min)] on drug particle size and morphology via anti-solvent sonocrystallization using the design of experiment approach. A six-factor, three-level experimental design using Taguchi’s L18 orthogonal array has been employed to obtain nano-range particle size of recrystallized drug at lab scale batch study. The particle size obtained using optimum conditions obtained by Taguchi method was further improved by Box–Behnken design. The optimum conditions obtained by Box–Behnken design were 1:3 solvent to anti-solvent ratio, 9.87 mL/min injection rate, 11.09 mg/mL drug concentration, 20 °C crystallization temperature, 8.6 min of sonication time, and 40% of sonication amplitude, which provided the optimized particle size of 143.6 nm. Various analytical tools were employed to characterize the sample obtained at the optimum condition. This statistical approach can further be explored to obtain nano-range particle size of other biopharmaceutical classification system class II drugs having poor water solubility via anti-solvent sonocrystallization.

Keywords: Ultrasound-assisted crystallization ; Taguchi ; Box–Behnken ; Telmisartan 

Full paper is available at

DOI: 10.1007/s11696-019-00886-8


Chemical Papers 74 (1) 323–331 (2020)

Monday, June 24, 2024

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