Effect of the mechanical activation on size reduction of crystalline acetaminophen drug particles

Esmaeil Biazar¹, Ali Beitollahi², S Mehdi Rezayat³, Tahmineh Forati⁴, Azadeh Asefnejad⁴, Mehdi Rahimi⁴, Reza Zeinali⁴, Mahmoud Ardeshir⁴, Farhad Hatamjafari¹, Ali Sahebalzamani⁴, Majid Heidari⁴

¹Chemistry Department, Islamic Azad University, Tonekabon Branch, Mazandaran, Iran; ²Material Department, Iran University of Science and Technology, Tehran, Iran; ³Department of Pharmacology, School of Medicine, Tehran University of Medical sciences, Tehran, Iran; ⁴Biomedicall Department, Islamic Azad University, Science and Research Branch, Tehran, Iran

Abstract: The decrease in particle size may offer new properties to drugs. In this study, we investigated the size reduction influence of the acetaminophen (C₈H₉O₂N) particles by mechanical activation using a dry ball mill. The activated samples with the average size of 1 µm were then investigated in different time periods with the infrared (IR), inductively coupled plasma (ICP), atomic force microscopy (AFM), and X-ray diffraction (XRD) methods. The results of the IR and XRD images showed no change in the drug structure after the mechanical activation of all samples. With the peak height at full width at half maximum from XRD and the Scherrer equation, the size of the activated crystallite samples illustrated that the AFM images were in sound agreement with the Scherrer equation. According to the peaks of the AFM images, the average size of the particles in 30 hours of activation was 24 nm with a normal particle distribution. The ICP analysis demonstrated the presence of tungsten carbide particle impurities after activation from the powder sample impacting with the ball and jar. The greatest reduction in size was after milling for 30 hours.

Keywords: acetaminophen, mechanical activation, structure investigation, nanoparticles, ball mill