Verification of the mixing processes of the active pharmaceutical ingredient, excipient and lubricant in a pharmaceutical formulation using a resonant acoustic mixing technology

摘要

Mixing processes are important for making high-quality pharmaceutical formulations and are related to dissolution and chemical stability in pharmaceutical manufacturing. The resonant acoustic? mixing (RAM) technology is a blending method, and it has been reported that it has a unique mixing action for various samples. In this study, in order to apply the RAM method to the pharmaceutical blending process, optimization of the operating conditions of RAM (acceleration and frequency) was conducted by numerical simulation. Powder mixing experiments were carried out using various RAM conditions and also a modified V-shaped mixing device with a powder material of theophylline powder and lactose or magnesium oxide and lactose. The angle of repose of the mixed powder sample was measured as an index of powder flowability and also the degree of powder mixing. A drug uniformity test of the mixed powders was performed to measure theophylline content using high-performance liquid chromatography. The results of these experiments indicate that the optimum values for acceleration and frequency in RAM mixing are 90–100 G and approximately 60 Hz, respectively, which prove the superiority of the RAM method over the ordinary mixing method. The RAM method was estimated to throw the powder upward into the air and perform mixing by utilizing free-fall, possibly by inducing a weightless state without depending on the density and mass of the sample. Therefore, RAM may be applicable to pharmaceutical manufacturing processes.