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The AAPS Journal

, Volume 15, Issue 3, pp 728–743 | Cite as

Engineered Mannitol Ternary Additives Improve Dispersion of Lactose–Salbutamol Sulphate Dry Powder Inhalations

  • Waseem Kaialy
  • Ali Nokhodchi
Research Article

Abstract

The aim of this study was to evaluate the influence of novel engineered fine mannitol particles (4.7%, w/w) on the performance of lactose–salbutamol sulphate dry powder inhaler (DPI) formulations to obtain promising aerosolisation properties. The results showed that the more elongated the fine mannitol particles, the weaker the drug–carrier adhesion, the better the drug content homogeneity, the higher the amount of drug expected to be delivered to the lower airways and the higher the total DPI formulation desirability. Linear relationships were established showing that mannitol particles with a more elongated shape generated powders with broader size distributions and that were less uniform in shape. The weaker the drug–carrier adhesion, the higher the fine particle fraction of the drug is upon aerosolisation. It is believed that more elongated fine mannitol particles reduce the number of drug–carrier and drug–drug physical contact points and increase the ability of the drug particles to travel into the lower airways. Additionally, a lower drug–carrier contact area, lower drug–carrier press-on forces and easier drug–carrier detachment are suggested in the case of formulations containing more elongated fine mannitol particles. Ternary ‘drug-coarse carrier-elongated fine ternary component’ DPI formulations were more favourable than both ‘drug-coarse carrier’ and ‘drug-elongated coarse carrier’ binary formulations. This study provides a comprehensive approach for formulators to overcome the undesirable properties of dry powder inhalers, as both improved aerosolisation performance and reasonable flow characteristics were obtained using only a small amount of elongated engineered fine mannitol particles.

KEY WORDS

added fines adhesive mixtures engineered fine mannitol formulation performance ternary component 

Abbreviations

ACM

Acetone crystallised mannitol

AR

Aspect ratio

CCM

Cooling crystallised mannitol

CI

Carr’s index

CM

Commercial mannitol

COD

Cutoff diameter

CV

Coefficient of variation

d10%

Particle diameter at 10% volume distribution

d50%

Particle diameter at 50% volume distribution (median diameter)

d90%

Particle diameter at 90% volume distribution

dae

Theoretical aerodynamic diameter

de

Geometric diameter (volume mean diameter)

di

Desirability function

ECM

Ethanol crystallised mannitol

ED

Emitted dose

DF

Overall desirability function

DPI

Dry powder inhaler

DSC

Differential scanning calorimetry

FMPs

Fine mannitol particles

FPF

Fine particle fraction

FPA

Fine particle aggregates

FR

Flatness ratio

GSD

Geometric standard deviation

HR

Hausner ratio

I + M

Inhaler with mouthpiece adaptor

IL

Impaction loss

IP

Induction port (throat)

MD

Mean diameter

MMAD

Mass median aerodynamic diameter

MSLI

Multistage liquid impinger

RH

Relative humidity

PSD

Particle size distribution

RD

Recovered dose

SDM

Spray dried mannitol

SE

Standard error

SEM

Scanning electron microscope

SF

Shape factor

SM

Supplementary material

SS

Salbutamol sulphate

PXRD

Powder X-ray diffraction

ρ

True density

Notes

ACKNOWLEDGMENTS

Waseem Kaialy thanks Dr. Ian Slipper (University of Greenwich) for taking the SEM images. The reviewers are thanked for their valuable comments.

Supplementary material

12248_2013_9476_MOESM1_ESM.docx (1.5 mb)
ESM 1 (DOCX 1.53 MB)

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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.Chemistry and Drug Delivery Group, Medway School of PharmacyUniversity of KentKentUK
  2. 2.Pharmaceutics and Pharmaceutical Technology Department, School of PharmacyUniversity of DamascusDamascusSyria
  3. 3.Drug Applied Research Center and Faculty of PharmacyTabriz University of Medical SciencesTabrizIran

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