Isothermal Dry Particle Coating (iDPC) – Dry Powder Inhaler (DPI) Formulations by Design: Controlled and Controllable Manufacture of Fixed Dose Combinations

Jasdip S Koner1, Shital Lungare1, Amandip Gill1, Rhys Jones1. David A Wyatt1,2 & Afzal Mohammed2

1Aston Particle Technologies, Aston Triangle, Birmingham, B4 7ET, United Kingdom

2Aston University, Aston Triangle, Birmingham, B4 7ET, United Kingdom

Summary

The current gold standard treatments for asthma and Chronic Obstructive Pulmonary Disease (COPD) involve the use of fixed dose combinations of highly potent agents to reach a range of therapeutic pathways synergistically. To prepare such formulations the pharmaceutical industry predominantly employs traditional technologies, often high shear blenders, with little advancement in the manufacturing process over the last 30 years. Such techniques are stochastic and difficult to control whilst imparting undesirable stress through local frictional heating and triboelectrification of the constituent materials. A novel manufacturing technology isothermal Dry Particle Coating (iDPC) through its unique operating principle at low shear, delivers the benefits of a high shear blender and consequently has wide applicability to DPI formulation. This study delivers intimate control of the manufacturing process using a Quality by Design (QbD) approach to the development and manufacture of triple fixed dose combination DPI formulations. Wide manufacturing design spaces using three defined critical process parameters (CPPs) were generated for two different triple combination formulations. iDPC delivers consistently acceptable blend homogeneity and controlled fine particle fraction (FPF) for each of the active pharmaceutical ingredients (APIs) within the formulation. In addition, the study shows that by altering the process parameters, good aerosolisation performance can be achieved without the requirement of force control agents. In conclusion this study demonstrates that iDPC delivers a controlled and predictable manufacturing process for the development of fixed dose combination DPI formulations and presents a viable new alternative to the antiquated gold standard manufacturing processes currently used across the industry.

Key Message

Isothermal Dry Particle Coating (iDPC) delivers a controlled and predictable manufacturing solution for fixed dose combinations DPIs through its unique mechanism of thin layer fluidisation.