Ultrasound Assisted Engineering of Lactose Crystals

To engineer lactose crystals of desired size, shape, surface and particle size distribution (PSD) as a carrier for dry powder inhalers (DPI) by ultrasound assisted in-situ seeding. Lactose crystals were obtained from solution by ultrasound assisted in-situ seeding, followed by growth in viscous glycerin solution. The crystals were characterized for physical properties and 63-90 mu m size fractions of different batches were mixed with salbutamol sulphate (SS) and compared for in-vitro deposition. Cooling crystallization with stirring for 10-20 h resulted in crystals with wide PSD and varied shape. Application of ultrasound resulted in rapid and complete crystallization in 5 min with rod-shaped fine crystals (15-30 mu m) and narrow PSD. In-situ seeded batches yielded micro-fine rod-shaped seed crystals. Seeding followed by growth in glycerin showed desirable size, high elongation ratio, smooth surface and narrow PSD, while growth under stirring showed high elongation ratio with rough surface. Crystals grown in glycerin showed highest dispersibility and fine particle fraction (FPF) of SS. Ultrasound assisted in-situ seeding, followed by ordered growth in glycerin offers rapid technique for separation of nuclei induction from crystal growth yielding desirable characteristics for better dispersion and in-vitro deposition when employed as DPI carrier.