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

• Published in: Pharmaceutical research 2011-04, Vol.28 (4), p.762-775
• Main Authors: Wauthoz, Nathalie, Deleuze, Philippe, Saumet, Amandine, Duret, Christophe, Kiss, Robert, Amighi, Karim
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; aerosol chemotherapy; Aerosols; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - chemistry; Antineoplastic Agents, Alkylating - therapeutic use; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chemotherapy; Dacarbazine - administration & dosage; Dacarbazine - analogs & derivatives; Dacarbazine - chemistry; Dacarbazine - therapeutic use; DPI; Drug Compounding; Drug Delivery Systems - instrumentation; Drug Delivery Systems - methods; Dry Powder Inhalers; Excipients - chemistry; General pharmacology; Humans; Lung cancer; lung neoplasms; Lung Neoplasms - drug therapy; Medical Law; Medical sciences; Microscopy, Electron, Scanning; Models, Theoretical; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Powders; pulmonary delivery; Research Paper; Solubility; Surface Properties; temozolomide; Tumors
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-010-0329-x

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.