Effects of co-milling on crystallinity of Salbutamol Sulphate using Adipic Acid

摘要

Particle size in pharmaceuticals is important in defining drug delivery and bioavailability in an increasing range of pharmaceutical applications. This formulation aspect affects performance of a drug product. It governs for instance, sedimentation and flocculation rates in suspensions, therapeutic effect of dry powder inhalations (DPI) and good powder homogeneity in tablets. Comminution is commonly used for this purpose and also to reduce particle size as it is difficult to achieve a narrow particle size distribution (PSD) via crystallization alone. However, milling also induces disorder in the crystal structure leading to the formation of amorphous regions, which are concentrated particularly at the surfaces of the particles (1-4). During post-milling storage, these amorphous regions are unstable and may transform back to the crystalline state. It is therefore important to monitor and control these process induced changes, as these also affect powder properties such as chemical and physical reactivity, dissolution and finally the drug product performance (5).