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

摘要

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 mixed in a high shear mixer (1L KG5) and samples are taken for time points of the blend and are checked with their corresponding colour points. This study investigates whether this colour method (IOCM) can predict or determine how much mixing is required for a Dry Powder Inhaler (DPI) blend (lactose/drug) to attain content uniformity (Real standard deviation (RSD) < 5). A High Shear Mixer (HSM) is used to mix DPI blends and samples were taken at different time points for different speeds and the content uniformity was tested. These time points were then compared with their corresponding colour points (lactose/iron oxide) to see if there is a correlation between colour points and content uniformity.