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Pharmaceutical Research

, Volume 25, Issue 12, pp 2835–2844 | Cite as

Ultrasound Assisted Engineering of Lactose Crystals

  • Ravindra S. Dhumal
  • Shailesh V. Biradar
  • Anant R. Paradkar
  • Peter York
Research Paper

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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 WORDS

dry powder inhaler particle engineering ultrasound assisted crystallization α-lactose monohydrate 

Abbreviations

A

area

ρbulk

bulk density

CC-1

cooling crystallization from lactose solution 30% w/w

CC-2

cooling crystallization from lactose solution 40% w/w

CC-3

cooling crystallization from lactose solution 50% w/w

CI

Carr’s index

DPI

dry powder inhaler

DSC

differential scanning calorimetry

ED

emitted dose

FPD

fine particle dose

FPF

fine particle fraction

ΔHd

enthalpy of dehydration of lactose obtained from the dehydration endotherm (J/g)

ΔHv

enthalpy of vaporization of water, 2,261 J/g

L

length

α-LM

α-lactose monohydrate

P

perimeter

PSD

particle size distribution

RD

recovered dose

RMMlactose

molecular mass of anhydrous lactose (340.3)

RMMwater

molecular mass of water (18.0)

SEM

scanning electron microscopy

Sono-1

crystallization of 30% w/w lactose solution with sonication for 5 min

Sono-2

crystallization of 40% w/w lactose solution with sonication for 5 min

Sono-3

crystallization of 50% w/w lactose solution with sonication for 5 min

Sono-G1

crystallization of 30% w/w lactose solution with sonication for 45 s followed by growth in glycerin

Sono-G2

crystallization of 40% w/w lactose solution with sonication for 45 s followed by growth in glycerin

Sono-G3

crystallization of 50% w/w lactose solution with sonication for 45 s followed by growth in glycerin

Sono-S1

crystallization of 30% w/w lactose solution with sonication for 45 s followed by stirring

Sono-S2

crystallization of 40% w/w lactose solution with sonication for 45 s followed by stirring

Sono-S3

crystallization of 50% w/w lactose solution with sonication for 45 s followed by stirring

SS

salbutamol sulphate

ρtap

tap density

TGA

thermogravimetric analysis

W

width

XRPD

X-ray powder diffractometry

Notes

Acknowledgements

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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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Ravindra S. Dhumal
    • 1
  • Shailesh V. Biradar
    • 1
  • Anant R. Paradkar
    • 1
    • 2
  • Peter York
    • 2
  1. 1.Department of PharmaceuticsBharati Vidyapeeth University, Poona College of Pharmacy and Research CentrePuneIndia
  2. 2.Institute of Pharmaceutical InnovationsUniversity of BradfordBradfordUK

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