Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2021-05-26 , DOI: 10.1007/s13346-021-01005-5 Manasi M Chogale 1 , Sagar B Dhoble 1 , Vandana B Patravale 1
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Inhalation route of drug delivery is the most favorable for pulmonary infections wherein direct drug delivery is desired to the lungs. Tuberculosis is one such infection suffering from poor therapeutic efficacy because of low patient compliance due to high drug dosing and lengthy treatment protocols. The current research work was undertaken to develop a dry powder inhaler (DPI) for administration of three first-line antitubercular antibiotics directly to the lungs to improve the treatment rates. Nanoformulations of isoniazid, pyrazinamide, and rifampicin were prepared, spray-dried to obtain a dry powder system, and blended with inhalation grade lactose to develop the DPI. The DPI was evaluated for its flow properties, pulmonary deposition, dissolution profile, and stability. The DPI possessed excellent flow properties with a fine particle fraction of 45% and a mass median aerodynamic diameter of approximately 5 µm indicating satisfactory lung deposition. In vitro drug release exhibited a sustained release of the formulations. In vivo studies showed a prolonged deposition in the lung at elevated concentrations compared to oral therapy. Stability studies proved that the formulation remained stable at accelerated and long-term stability conditions. The DPI could complement the existing oral therapy in enhancing the therapeutic efficacy in patients.
Graphical abstract
中文翻译：
用于结核病的三重组合“纳米”干粉吸入器：体外和体内肺部特征
药物递送的吸入途径对于需要将药物直接递送至肺部的肺部感染是最有利的。结核病是一种治疗效果差的感染，因为高药物剂量和冗长的治疗方案导致患者依从性低。目前的研究工作是开发一种干粉吸入器（DPI），用于将三种一线抗结核抗生素直接给药于肺部，以提高治疗率。制备异烟肼、吡嗪酰胺和利福平的纳米制剂，喷雾干燥得到干粉体系，并与吸入级乳糖混合以开发DPI。评估了 DPI 的流动特性、肺沉积、溶出曲线和稳定性。DPI 具有出色的流动特性，细颗粒分数为 45%，质量中值空气动力学直径约为 5 µm，表明肺沉积令人满意。体外药物释放表现出制剂的持续释放。体内研究表明，与口服治疗相比，浓度升高时肺中的沉积时间延长。稳定性研究证明，该制剂在加速和长期稳定条件下保持稳定。DPI 可以补充现有的口服疗法以提高患者的治疗效果。体内研究表明，与口服治疗相比，浓度升高时肺中的沉积时间延长。稳定性研究证明，该制剂在加速和长期稳定条件下保持稳定。DPI 可以补充现有的口服疗法以提高患者的治疗效果。体内研究表明，与口服治疗相比，浓度升高时肺中的沉积时间延长。稳定性研究证明，该制剂在加速和长期稳定条件下保持稳定。DPI 可以补充现有的口服疗法以提高患者的治疗效果。
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