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Temozolomide-Based Dry Powder Formulations for Lung Tumor-Related Inhalation Treatment

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ABSTRACT

Purpose

Temozolomide dry powder formulations for inhalation, performed with no excipient or with a lipid or lactose coating, have been evaluated.

Methods

The particle size of raw temozolomide in suspension was reduced by a high-pressure homogenizing technique, and the solvent was evaporated by spray-drying to obtain a dry powder. The physicochemical properties of this powder were evaluated and included its crystalline state, thermal properties, morphology, particle size and moisture and drug content, and these properties were determined by X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, laser light scattering, thermogravimetric analysis and high-performance liquid chromatography, respectively. The aerodynamic properties and release profiles were also evaluated using a multistage liquid impinger and a modified USP type 2 dissolution apparatus adapted for inhaler products, respectively.

Results

The dry powder inhalation formulations had a high temozolomide content that ranged from 70% to 100% in the crystalline state and low moisture content. Aerodynamic evaluations showed high fine-particle fractions of up to 51% related to the metered dose. The dissolution profile revealed a similarly fast temozolomide release from the formulations.

Conclusions

Dry temozolomide powder formulations, based on the use of acceptable excipients for inhalation and showing good dispersion properties, represent an attractive alternative for use in local lung cancer therapy.

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Abbreviations

DLPC:

1,2-dilauroyl-sn-glycero-3-phosphocholine

DMPC:

1,2-dimyristoyl-sn-glycero-3-phosphocholine

DPI:

dry powder inhaler

DPPC:

dipalmitoyl phosphatidylcholine

DSC:

differential scanning calorimetry

FPD:

fine particle dose

FPF:

fine particle fraction

HPH:

high-pressure homogenizing

HPLC:

high-performance liquid chromatography

HPMC:

hypromellose

IV:

intravenous

MMAD:

mass median aerodynamic diameter

MsLI:

multi-stage liquid impinger

MTIC:

5-(3-methyltriazen-1-yl)imidazole-4-carboxamide

NGI:

next generation impactor

NSCLC:

non-small cell lung cancer

P90H:

phospholipon 90H

SCLC:

small cell lung cancer

SEM:

scanning electron microscopy

SLF:

simulated lung fluid

TGA:

thermogravimetric analysis

TMZ:

temozolomide

XRPD:

X-ray powder diffraction

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ACKNOWLEDGMENTS

The authors would like to thank the Industrial Chemistry Department of ULB for the X-Ray Powder Diffraction. Robert Kiss is a Director of Research with the Fonds National de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium).

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Authors and Affiliations

  1. Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium

    Nathalie Wauthoz, Philippe Deleuze, Amandine Saumet, Christophe Duret & Karim Amighi

  2. Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium

    Robert Kiss

  3. Laboratory of Pharmaceutics and Biopharmaceutics Faculty of Pharmacy,, ULB, Boulevard du Triomphe - CP207 Campus de la Plaine, 1050, Brussels, Belgium

    Nathalie Wauthoz

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  1. Nathalie Wauthoz
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  2. Philippe Deleuze
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Correspondence to Nathalie Wauthoz.

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Wauthoz, N., Deleuze, P., Saumet, A. et al. Temozolomide-Based Dry Powder Formulations for Lung Tumor-Related Inhalation Treatment. Pharm Res 28, 762–775 (2011). https://doi.org/10.1007/s11095-010-0329-x

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  • DOI: https://doi.org/10.1007/s11095-010-0329-x

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