The Influence of Mechanical Processing of Dry Powder Inhaler Carriers on Drug Aerosolization Performance

Lactose characteristics and the generation of the aerosol

“…In general, milled lactose has a significant effect on the FPF of drugs. These effects are predominantly attributed to the fines content, showing a strong correlation between increased fines and FPF (see Section 4.1.2.1) [70]. However, increased particle aggregation may occur following particle-size reduction.…”

“…Moreover, analysis of the fines concentration with respect to mill time has indicated a significant increase from 4.4% to 18.0% for between 0 and 60 min of mill time. In fact, it has been suggested that cleavage planes, commonly found in crystals, fracture into many fine particles [70]. In general, milled lactose has a significant effect on the FPF of drugs.…”

“…Larger particles may arch and protect smaller particles from impact, whilst smaller particles coat the grinding medium and cushion the larger particles from impact. This protection may prevent further particle-size reduction [70].…”

“…Intense milling can cause unwanted change in the physico-chemical properties of the material, e.g., creation of amorphous regions at the surface, which can affect hygroscopicity and stability, electrostatic charging and cohesivity [72]. It has been demonstrated that an increase in mill time results in an exponential increase in amorphous content [70]. In addition, the micronisation process leads to small, irregularly shaped flat lactose particles, and extensive flat surfaces promote large contact areas, resulting in increased adhesion between the particles and therefore poor flow properties [2].…”

Lactose Composite Carriers for Respiratory Delivery

“…Inter-particle adhesion in carrier-based DPI systems may be attributed to multiple factors including surface energy (3), relative humidity (4-7), morphology of the API (8)(9)(10), the presence of ternary components (11)(12)(13) and morphology of the carrier (14)(15)(16). To complicate matters, the lack of homogeneity across the surface of a carrier results in a distribution of adhesion forces which may be classified as isoenergetic regions or 'active sites' (2,17).…”