The development of powder pocket dynamic mechanical analysis for the detection of amorphous content in salbutamol sulphate: a feasibility study

Abstract

Dry powder inhalers are a commonly prescribed dosage form for the treatment of asthma. In essence they consist of an active compound in particulate form (1–5 m diameter) adhered loosely on the surface of a larger inert particle, usually lactose (25–60 m diameter). Processing of the pharmaceutical active powder to produce the stated particle size range requires high-energy milling or micronisation. However, this process also breaks down the surface crystalline structure of the particles, introducing an unstable amorphous phase to the powder. This conversion of the crystalline to the amorphous state can be of great pharmaceutical significance. It can influence the bioavailability, stability, formulation and manufacturing of the medicinal product. The milling-induced amorphism must be detected and quantified to prevent stability and formulation consequences. The objective of this study was to evaluate the feasibility of using the novel technique of powder pocket dynamic mechanical analysis (DMA) to detect and quantify amorphous content in pharmaceutical powders. Mixtures of amorphous and crystalline salbutamol sulphate were used as test materials.