Use of Co-milling to Improve Physical Stability of Amorphous Salbutamol Sulphate

In recent years, co-milling of active pharmaceutical ingredients (APIs) with excipients is being investigated as a promising technique to improve desired properties such as solubility and dissolution profiles, bioavailability, aerosolization and physical stability. Traditionally, excipients are simply blended into a drug formulation to improve the manufacturability or product quality, e.g. to improve the ease of tablet compaction, to increase solubility or bioavailability. As milling is an energy intensive process, it tends to induce structural disorders leading to the formation of amorphous regions, which are located particularly at the surfaces of milled particles. This amorphous phase possesses high molecular mobility and tends to revert back to the more stable crystalline state upon storage. Stabilization of this amorphous form is important because this solid-state change can be detrimental to the drug performance as it affects critical particle properties such as morphology, particle size distribution, specific surface area, chemical and physical reactivity and dissolution rates.