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Formulation Development and In Vivo Evaluation of a New Dry Powder Formulation of Albuterol Sulphate in Beagle Dogs

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ABSTRACT

Purpose

Study objectives were to develop, characterize, and evaluate a novel excipient for dry powder inhalation formulations in a canine model with a model compound.

Methods

Dry powder inhalation formulations of albuterol sulphate were developed and compared to a commercially available nebulizer albuterol solution formulation. In vitro analysis indicated a high fine-particle fraction (FPF, >70%) and a respirable particle size (∼2.5 µm MMAD). Each inhalation formulation, including controls, was delivered targeting a deposited lung dose of 10 µg/kg albuterol. Active formulations were evaluated for pharmacokinetic (PK) profile and bronchodilatory effects in a ragweed-sensitized dog model of allergic airway responses.

Results

In vitro, the dextran spray-dried formulated materials showed that aerosol performance, including FPF, MMAD, glass transition temperature, and amorphous characteristics, were all largely unaffected by amount of drug loaded. Both the commercial and the dry powder formulations attenuated the ragweed-induced bronchoconstriction by 91.59 ± 3.60 and 81.28 ± 9.29%, respectively. The PK profiles for both albuterol formulations were similar, as were the corresponding Tmax, Cmax and T1/2.

Conclusions

Results indicate that dextran 10 has promise as a novel excipient for dry powder inhalation drug delivery, in a preclinical setting, over a wide range of drug loadings.

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Abbreviations

ANOVA:

analysis of variance

APS:

Aerodynamic Particle Sizer

COPD:

chronic obstructive pulmonary disorder

DC:

dendritic cell

DVS:

dynamic vapor sorption

FPF:

fine particle fraction

GSD:

geometric standard deviation

HPLC-UV:

high-pressure liquid chromatography-ultra violet

LC-MS-MS:

liquid chromatography tandem mass spectrometry

LRRI:

Lovelace Respiratory Research Institute

MDI:

metered dose inhaler

mDSC:

modulated differential scanning calorimetry

MMAD:

mass median aerodynamic diameter

NGI:

Next Generation Impactor

PK:

pharmacokinetic

PSD:

particle size distribution

PXRD:

powder X-ray diffraction

RH:

relative humidity

RW:

ragweed

SEM:

scanning electron microscopy, standard error of the mean

SPE:

solid phase extraction

Tg:

glass transition temperature

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Authors and Affiliations

  1. Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, New Mexico, 87108, USA

    Philip J. Kuehl, Edward G. Barrett, Jacob D. McDonald & Karin Rudolph

  2. Bend Research Inc., 64550 Research Road, Bend, Oregon, 97701-8599, USA

    David Vodak, Dan Dobry & David Lyon

Authors
  1. Philip J. Kuehl
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  2. Edward G. Barrett
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  3. Jacob D. McDonald
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  4. Karin Rudolph
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  5. David Vodak
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  6. Dan Dobry
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  7. David Lyon
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Corresponding author

Correspondence to Philip J. Kuehl.

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Kuehl, P.J., Barrett, E.G., McDonald, J.D. et al. Formulation Development and In Vivo Evaluation of a New Dry Powder Formulation of Albuterol Sulphate in Beagle Dogs. Pharm Res 27, 894–904 (2010). https://doi.org/10.1007/s11095-010-0084-z

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  • DOI: https://doi.org/10.1007/s11095-010-0084-z

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