Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Brussels, Belgium.
Eur J Pharm Biopharm. 2010 Nov;76(3):454-63. doi: 10.1016/j.ejpb.2010.08.005. Epub 2010 Aug 24.
The aim of this work was to develop highly dispersible and dry formulations of insulin for use in dry powder inhalers (DPIs) using high-pressure homogenisation (HPH) and spray-drying. Several formulations were evaluated, including formulations spray-dried without excipients and formulations coated with lipids. A physiological lipid composition based on a mixture of cholesterol and phospholipids was used to form the coating film around micronised drug particles. The production technique and excipients were chosen in order to limit the degradation of the active ingredient. The resulting powders exhibited a size and shape suitable for the deep lung deposition of drugs, and good aerodynamic features were obtained for the different formulations tested, with fine particle fractions between 46% and 63% vs. 11% for raw insulin powder. The presence of a lipid coating of up to 30% (w/w) did not significantly affect the aerodynamic behaviour, and the coated formulations also exhibited a decreased residual moisture content of between 2.3% and 3.7% vs. 4.8% for raw insulin, which should improve the long-term stability of the protein formulations. No degradation of the insulin molecule occurred during the HPH/spray-drying process, as it was shown using an HPLC method (insulin content between 98.4% and 100.5%), and the content in high molecular weight proteins, assessed using a gel filtration method, stayed below 0.4%.
这项工作的目的是开发高分散性和干燥的胰岛素制剂，用于干粉吸入器（DPIs），采用高压均质（HPH）和喷雾干燥。评估了几种制剂，包括无赋形剂喷雾干燥的制剂和包被脂质的制剂。使用基于胆固醇和磷脂混合物的生理脂质组合物在微米化药物颗粒周围形成包衣膜。选择生产技术和赋形剂是为了限制活性成分的降解。所得粉末具有适合药物深肺沉积的大小和形状，并且不同测试制剂的空气动力学特性良好，与原始胰岛素粉末的 11%相比，细颗粒分数在 46%至 63%之间。高达 30%（w/w）的脂质包衣的存在不会显著影响空气动力学行为，并且包被的制剂的残留水分含量也降低了 2.3%至 3.7%，与原始胰岛素的 4.8%相比，这应该提高蛋白质制剂的长期稳定性。如使用 HPLC 方法（胰岛素含量在 98.4%至 100.5%之间）所示，在 HPH/喷雾干燥过程中胰岛素分子没有降解，并且使用凝胶过滤法评估的高分子量蛋白质含量保持在 0.4%以下。
