依达拉奉和利培酮的电加热气化吸入给药研究

Study on Inhalation of Edaravone and Risperidone by Electrical Heating Vaporization

与传统干粉吸入剂直接吸入含药粉体不同,电加热气化吸入给药是将药物快速升温气化,随后在吸气气流中冷却形成气溶胶而吸入。因此,在受热气化过程中控制药物的降解程度,同时保证形成的气溶胶具有较好的递送效率是重要的研究内容。本研究选取依达拉奉(低熔点和沸点)和利培酮(高熔点和沸点)为模型药,采用自制的快速升温、可调式电加热吸入装置,对不锈钢薄片材质、药物涂层厚度、加热气化温度进行优化,探索药物气化吸入过程中控制热降解和提升递送效果的方法。结果表明,不锈钢薄片经500℃、30 min加热处理后可显著提高利培酮气溶胶纯度,从39.31%提高到95.77%。1.9 mg依达拉奉在311和357℃的加热气化温度下,递送药量较高,气溶胶纯度大于99.8%;而利培酮0.5 mg在357℃的加热气化温度下,递送药量和气溶胶纯度均较高。2种药物经电加热气化后微细粒子分数均大于95%,具有较好的肺部递送特性。

Unlike traditional dry powder inhalers that provide directly inhalable drug-containing powders,the electrical heating vaporization inhalation device vaporizes the drug through rapid heating,then makes the drug cool in the inspiratory airflow to form aerosol to be inhaled.Therefore,it is critical to control the degree of drug degradation in the process of vaporization and ensure that the formed aerosol has good delivery efficiency.This study was conducted by the self-made rapid heating and adjustable electrical heating vaporization device with edaravone(with low melting point and boiling point)and risperidone(with high melting point and boiling point)as the model drugs.The stainless steel sheet material,drug-coating layer thickness and heating vaporization temperature were optimized to control thermal degradation and improve delivery efficiency.The results showed that the purity of risperidone aerosol could be significantly increased from 39.31%to 95.77%after the stainless steel sheet was treated at 500℃for 30 min.Edaravone with drug loading of 1.9 mg had high emitted doses and aerosol purity(above 99.8%)at the vaporization temperatures of 311 and 357℃.At the vaporization temperature of 357℃,risperidone with a drug loading of 0.5 mg also showed high emitted doses and aerosol purity.And the fine particle fraction(FPF)of both model drugs through electrical heating vaporization inhalation were over 95%,indicating good lung delivery characteristics.