caa a22 4500 44531348X CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s11095-010-0329-x doi (NATIONALLICENCE)springer-10.1007/s11095-010-0329-x Temozolomide-Based Dry Powder Formulations for Lung Tumor-Related Inhalation Treatment [Elektronische Daten] [Nathalie Wauthoz, Philippe Deleuze, Amandine Saumet, Christophe Duret, Robert Kiss, Karim Amighi] 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. Springer Science+Business Media, LLC, 2010 aerosol chemotherapy nationallicence DPI nationallicence lung cancer nationallicence pulmonary delivery nationallicence temozolomide nationallicence DLPC : 1,2-dilauroyl-sn-glycero-3-phosphocholine nationallicence DMPC : 1,2-dimyristoyl-sn-glycero-3-phosphocholine nationallicence DPI : dry powder inhaler nationallicence DPPC : dipalmitoyl phosphatidylcholine nationallicence DSC : differential scanning calorimetry nationallicence FPD : fine particle dose nationallicence FPF : fine particle fraction nationallicence HPH : high-pressure homogenizing nationallicence HPLC : high-performance liquid chromatography nationallicence HPMC : hypromellose nationallicence IV : intravenous nationallicence MMAD : mass median aerodynamic diameter nationallicence MsLI : multi-stage liquid impinger nationallicence MTIC : 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide nationallicence NGI : next generation impactor nationallicence NSCLC : non-small cell lung cancer nationallicence P90H : phospholipon 90H nationallicence SCLC : small cell lung cancer nationallicence SEM : scanning electron microscopy nationallicence SLF : simulated lung fluid nationallicence TGA : thermogravimetric analysis nationallicence TMZ : temozolomide nationallicence XRPD : X-ray powder diffraction nationallicence Wauthoz Nathalie Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut Deleuze Philippe Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut Saumet Amandine Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut Duret Christophe Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut Kiss Robert Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium aut Amighi Karim Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 762-775 0724-8741 28:4<762 2011 28 11095 https://doi.org/10.1007/s11095-010-0329-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0329-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wauthoz Nathalie Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut NATIONALLICENCE 700 1- Deleuze Philippe Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut NATIONALLICENCE 700 1- Saumet Amandine Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut NATIONALLICENCE 700 1- Duret Christophe Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut NATIONALLICENCE 700 1- Kiss Robert Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium aut NATIONALLICENCE 700 1- Amighi Karim Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie,, Université Libre de Bruxelles (ULB), Brussels, Belgium aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 762-775 0724-8741 28:4<762 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer