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Pharmaceutical Research

, Volume 25, Issue 7, pp 1583–1590 | Cite as

A Comparison of the Pulmonary Bioavailability of Powder and Liquid Aerosol Formulations of Salmon Calcitonin

  • Andrew Clark
  • Mei-chang Kuo
  • Stephen Newman
  • Peter Hirst
  • Gary Pitcairn
  • Matt Pickford
Research Paper

Abstract

Purpose

To compare the pulmonary pharmacokinetics and relative bioavailability of salmon calcitonin delivered as aqueous droplets, pH 6.6 and pH 4.8 with that of a spray dried powder in healthy volunteers.

Methods

Spray dried powders (1.6 μm [GSD 2.1]) containing 5% by wt. sCal, 6.25% human serum albumin, 73.55% mannitol and 15% citric acid/sodium citrate were prepared using a Buchi model 190 spray drier. Aqueous solutions were prepared by dissolving the spray dried powder at a sCal concentration of 1.25 mg/ml, pH was adjusted using 21 mM sodium hydroxide. Aerosols were delivered as part of a 4 way cross-over study to 16 healthy volunteers. The Nektar pulmonary delivery device was used to deliver the dry powder aerosol. A Salter nebulizer controlled by a Rosenthal dosimeter was used to deliver the aqueous aerosols. Miacalcin™ injection was used as the subcutaneous control. Dose delivered to the lung was estimated by gamma scintigraphy. Plasma concentrations of sCal were measured using a radioimmunoassay.

Results

Aerosol size distributions were matched, 3.3 μm MMAD and ∼2.2 GSD. Inhaled flow rates were similar, although not equal, 5.8 and ∼9.8 l/min respectively for dry powder and liquid inhalations. Lung doses of sCal ranged from 53 to 88 μgm, peripheral lung doses from 25 to 51 μgm. Pharmacokinetic profiles and lung bioavailability relative to subcutaneous injection for all formulations were similar (not statistically significantly different p > 0.05), relative lung bioavailability ranged from 11% to 18%, estimates of relative bioavailability based on peripheral lung dose ranged from 20% to 33%.

Conclusion

The study showed no difference in pharmacokinetic profiles between the various aerosol dosage forms. pH of the aqueous solutions did not affect kinetics or relative bioavailability.

Key words

aerosol bioavailability deposition dry powder nebulizer salmon calcitonin 

Abbreviations

ACI

Andersen impactor

AUC

area under the curve

BAV

bioavailability

C

central

DCU

dose content uniformity

GSD

geometric standard deviation

HPLC

high pressure liquid chromatograph

MMAD

mass median aerodynamic diameter

P

peripheral

P/C

ratio, peripheral to central ratio

PDS

Nektar pulmonary delivery system

PSD

particle size distribution

sCal

salmon calcitonin

SD

standard deviation

USP

united States Pharmacopeia

VMD

volume median diameter

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Andrew Clark
    • 1
  • Mei-chang Kuo
    • 1
  • Stephen Newman
    • 2
    • 3
  • Peter Hirst
    • 2
    • 4
  • Gary Pitcairn
    • 2
    • 5
  • Matt Pickford
    • 2
    • 6
  1. 1.Nektar TherapeuticsSan CarlosUSA
  2. 2.Pharmaceutical Profiles Ltd.NottinghamEngland
  3. 3.Scientific ConsultantNottinghamEngland
  4. 4.Vectura Group plcNottinghamEngland
  5. 5.Pfizer Global R&DSandwichKent
  6. 6.AstraZenecaLoughboroughEngland

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