Analysis of pin milling of pharmaceutical materials

Abstract

Milling is an important process for tailoring the particle size distribution for enhanced dissolution, content uniformity, tableting, etc., specially for active pharmaceutical ingredients and excipient in pharmaceutical industries. Milling performance of particulate solids depends on the equipment operating conditions (geometry, process conditions and input energy etc.) as well as material properties (particle size, shape, and mechanical properties, such as Young's modulus, hardness and fracture toughness). In this work, a newly developed approach to assess the breakability of pharmaceutical materials using an aerodynamic dispersion method has been combined with the Discrete Element Method (DEM) to simulate the dynamic behaviour of a number of pharmaceutical materials in a pin mill. A sensitivity analysis is carried out addressing the effect of the milling conditions (rotational speed of the mill and feed particle flow rate) and feed properties on the milled products in terms of the shift in the specific surface area of the milled particles. The outcome of the work is used as a method to predict the breakage of the particles for the milling conditions where chipping takes place.

Particle breakability assessment using an Aero S disperser

“…Using a small sample quantity, short duration of the test and availability of the device are advantageous for evaluating the breakability of the materials. The information obtained in this way can be used to predict the milling behaviour of the material in mill types, in which mechanical stressing is due to impact (Bonakdar and Ghadiri, 2018).…”

“…Fulchini et al (2017) also used the same technique to evaluate the attrition propensity of Chemical Looping Catalyst, where the particulate solids circulate between two fluidised beds, in which the solids undergo alternate chemical oxidation to chemical reduction and experience attrition. Bonakdar and Ghadiri (2018) used the breakage kernels obtained by the Scirocco disperser to predict the size reduction of pharmaceutical materials in a pin mill.…”

Effect of Mixer Type on Particle Coating by Magnesium Stearate for Friction and Adhesion Modification

“…The surfaces of α-LM are very energetic with heterogeneous energy distribution, referred to as hot spots [ 27 ]. They attract a considerable amount of very fine particles of the same material, due to attrition during manufacturing, herein referred to as debris [ 28 ]. In fact, for dry powder inhalation, additional fine α-LM powder is often added to blind these hot spots, so that the adhesion and detachment of the active pharmaceutical ingredients are more controllable [ 29 ].…”

Psilocybin: Characterization of the Metastable Zone Width (MSZW), Control of Anhydrous Polymorphs, and Particle Size Distribution (PSD)

“…Third, there was the need to control the PSD, which is well known in the industry. − However, an efficient method such as dry milling using a fluid energy mill or mechanical impact comes with an increased cost of processing and a potential decrease in yield. Due to the significant mass loss on dehydration of the trihydrate polymorph, the anhydrous polymorph crystal has been observed as fragile.…”