Physics

Work in process

Process analytical technology

Process engineering

Pharmaceutical manufacturing

Mechanics

Bioinformatics

Biology

Operating system

Epistemology

Engineering

Philosophy

Particle size

Discrete element method

Geotechnical engineering

Operations management

Quality (philosophy)

Pharmaceutical industry

Computer science

Critical quality attributes

Granulation

Process (computing)

Chemical engineering

Medicine

Pharmacology

Pharmaceutics

Process simulation using mathematical modeling tools is becoming more common in the pharmaceutical industry. A mechanistic model is a mathematical modeling tool that can enhance process understanding, reduce experimentation cost and improve product quality. A commonly used mechanistic modeling approach for powder is the discrete element method (DEM). Most pharmaceutical materials have powder or granular material. Therefore, DEM might be widely applied in the pharmaceutical industry. This review focused on the basic elements of DEM and its implementations in pharmaceutical manufacturing simulation. Contact models and input parameters are essential elements in DEM simulation. Contact models computed contact forces acting on the particle-particle and particle-geometry interactions. Input parameters were divided into two types-material properties and interaction parameters. Various calibration methods were presented to define the interaction parameters of pharmaceutical materials. Several applications of DEM simulation in pharmaceutical manufacturing processes, such as milling, blending, granulation and coating, were categorized and summarized. Based on this review, DEM simulation might provide a systematic process understanding and process control to ensure the quality of a drug product.

Application of the Discrete Element Method for Manufacturing Process Simulation in the Pharmaceutical Industry