Investigation of the role of balls in Aprepitant micronization by ball milling method

Abstract

Introduction: Formulating drugs with low aqueous solubility in considered as one of the biggest challenges of pharmaceutical industry. One of the widely used approaches in improving the solubility of low aqueous solubility drugs is particle size reduction, also known as micronization. Ball milling is a mechanical, top-down technic used in pharmaceutical particle size reduction. Various factors play a role in properties of obtained particles. In this study, the effect of some of these factors on properties of milled drug particles is evaluated. Objective: Investigation of the effect of the ball number and ball size used in the micronization of Aprepitant by ball milling method Method: Aprepitant was chosen as the model drug. Two factors with three levels (Size and number of balls) and a factor with two levels (milling speed) was created as a full factorial design. The initial suspension was made by suspending the drug in distilled water using excepiants. The coarse suspension was milled in planetary ball mill. The obtained suspension was measured using a particle size analyzer. The results were analyzed by Minitab software. Results: The ball size, ball number and speed mill were effective on mean value of volume distribution, PSD D90% and mean value of volume distribution to mean value of number distribution ratio. Greater ball number and higher milling speed lead to lower mean value of volume distribution, lower PSD D90% and lower mean value of volume distribution to mean value of number distribution ratio. All three parameters showed an increase with larger ball size. Conclusion: Ball size, ball number and milling speed are three effective factors in process of ball milling. By increasing ball number and decreasing ball size, better micronization of drug particle takes place and the particle size is more uniform.