Laboratoire de Pharmacie Galénique et de Biopharmacie Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Pharm Res. 2011 Apr;28(4):762-75. doi: 10.1007/s11095-010-0329-x. Epub 2010 Nov 30.
Temozolomide dry powder formulations for inhalation, performed with no excipient or with a lipid or lactose coating, have been evaluated.
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.
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.
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.
评估了用于吸入的无赋形剂或含脂质或乳糖包衣的替莫唑胺干粉制剂。
通过高压匀质技术减小混悬液中替莫唑胺原料药的粒径，并通过喷雾干燥蒸发溶剂以获得干粉。评估了该粉末的物理化学性质，包括其晶体状态、热性能、形态、粒径、水分和药物含量，并通过 X 射线粉末衍射、差示扫描量热法、扫描电子显微镜、激光光散射、热重分析和高效液相色谱法分别测定了这些性质。还分别使用多阶段液体撞击器和适用于吸入器产品的改良 USP 第 2 型溶解装置评估了空气动力学性质和释放曲线。
干粉吸入制剂的替莫唑胺含量很高，在晶体状态下为 70%至 100%，水分含量低。空气动力学评估显示高达 51%的细颗粒分数与计量剂量相关。溶解曲线显示制剂中替莫唑胺的释放速度也很快。
基于可接受的吸入赋形剂且显示良好分散性能的替莫唑胺干粉制剂，为局部肺癌治疗提供了一种有吸引力的替代方案。
