Ultrasound Assisted Engineering of Lactose Crystals
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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 μm 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 μm) 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.
KEY WORDSdry powder inhaler particle engineering ultrasound assisted crystallization α-lactose monohydrate
cooling crystallization from lactose solution 30% w/w
cooling crystallization from lactose solution 40% w/w
cooling crystallization from lactose solution 50% w/w
dry powder inhaler
differential scanning calorimetry
fine particle dose
fine particle fraction
enthalpy of dehydration of lactose obtained from the dehydration endotherm (J/g)
enthalpy of vaporization of water, 2,261 J/g
particle size distribution
molecular mass of anhydrous lactose (340.3)
molecular mass of water (18.0)
scanning electron microscopy
crystallization of 30% w/w lactose solution with sonication for 5 min
crystallization of 40% w/w lactose solution with sonication for 5 min
crystallization of 50% w/w lactose solution with sonication for 5 min
crystallization of 30% w/w lactose solution with sonication for 45 s followed by growth in glycerin
crystallization of 40% w/w lactose solution with sonication for 45 s followed by growth in glycerin
crystallization of 50% w/w lactose solution with sonication for 45 s followed by growth in glycerin
crystallization of 30% w/w lactose solution with sonication for 45 s followed by stirring
crystallization of 40% w/w lactose solution with sonication for 45 s followed by stirring
crystallization of 50% w/w lactose solution with sonication for 45 s followed by stirring
X-ray powder diffractometry
Anant R. Paradkar is thankful to British Council for UK-India Education and Research Initiative (UKERI) Fellowship, Bharati Vidyapeeth University, Pune for the sabbatical leave and AICTE (New Delhi, India) for grant in the form of Research Promotion Scheme. Ravindra S. Dhumal and Shailesh V. Biradar are thankful to CSIR (New Delhi, India) for providing financial support in the form of Senior Research Fellowship (SRF). Authors acknowledge the support of Cipla Ltd, (Mumbai, India), DMV International (The Netherlands) and Universal Capsules (Mumbai, India) for providing gift samples of salbutamol sulphate, lactose monohydrate and hard gelatin capsules, respectively. Authors are thankful to Dr. P. K. Khanna, Head, Nano Science group, Centre for Materials for Electronic Technology (C-MET), Pune, India for providing the facilities at C-MET.
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