464728 Improving the Mixing Process of Dry Powder Inhaler Formulations with the Iron Oxide Colour Method

Tuesday, November 15, 2016: 2:18 PM
Bay View (Hotel Nikko San Francisco)
Kahlil Desai1, Karen Hapgood1, David Morton2, Peter Stewart2 and David Barling3, (1)Chemical Engineering, Monash University, Clayton, Australia, (2)Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Parkville, Australia, (3)GlaxoSmithKline Australia, Melbourne, Australia

Blending of one or more powders is critical for many pharmaceutical powders, including formulations used for Dry Powder Inhalers. Dry powder inhalers (DPIs) are mixed dry powder medications (asthma) administered via the lungs (pulmonary route). DPIs generally comprise 1% of API and 99% lactose and are mixed in a tumbler mixer or a high shear mixer. Due to empirical nature of commercial production there are production issues such as failed batches, content uniformity issues, and product performance failures, especially low inhalation efficiency values. This leads to production and economic losses but also a lack of understanding in the blending process.

The iron oxide colour method (IOCM) is a recent technique that involved mixing 1% of red iron oxide and 99% of lactose in different mixers and observing the colour [1]. The colour of the blend indicates how mixed the blend is; as the mixing time continues the blend colour changes from pink to red to orange; this method helps to understand the mixing process and the quality of mixing. This work follows on with the method by mixing and testing DPI formulations. Actual DPI blends, 99% DPI grade lactose and 1% API (salbutamol sulphate) are either mixed in a tumbler (Turbula T2C) or a high shear mixer (1L KG5) and samples are taken for time points of the blend and are checked with their corresponding colour points.

The ultimate goal of the project is to use the iron oxide colour method to give information on the quality of mixing of API-lactose blends from different mixers and aid scale up and technical transfer of pharmaceutical DPI manufacturing.

[1] D. Barling, D.A.V. Morton, K. Hapgood, Pharmaceutical dry powder blending and scale-up: Maintaining equivalent mixing conditions using a coloured tracer powder, Powder Technology, (2014).

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