السنة | 2020-01-29 |
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التخصص | ماجستير العلوم الصيدلانية |
العنوان | Nanoparticle Carriers for targeted pulmonary drug delivery |
اسم المشرف الرئيسي | ايمان درويش مصباح الزميلي | Eman Al-zmaily |
اسم المشرف المشارك | | |
اسم الطالب | شهد فؤاد الطراونة | Shahd Fuad Al-tarawneh |
Abstract | The pulmonary route for drug delivery offers multiple advantages over other routes of drug administration owing to its large surface area, high vascularization and thin blood-alveolar barrier. Drug delivery by this route is convenient to patients, less painful (non-invasive) and can be employed for local and systemic delivery of active pharmaceutical ingredients (APIs). The use of dry powder inhalers (DPI) enables the delivery of APIs to the lung with favorable properties. To do that, powder should possess critical quality attributes pertinent to size, flowability and ability to reach the lower parts of the respiratory system. Nano aggregate formulations are suitable technology that enables the development of successful DPIs. Therefore, the aim of this project is to employ Nano technology to develop iron oxide containing nanoparticles using model API- dactinomycin. Iron oxide nanoparticles will serve as a carrier for directing the API to the targeted site of action within the lung. The development and optimization of iron oxide nanoparticles was carried out employing Quality by Design (QbD) methodology. Nanoparticles were built up from iron oxide that was chemically prepared using bottom up method. Two polymers were investigated (chitosan and sodium alginate). The quantitative method for the analysis of dactinomycin by HPLC was validated according ICH guidelines. That was followed by screening studies for iron oxide nanoparticles development. The produced dactinomycin containing nanoparticles was characterized for mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst effect, iron oxide FPF and the emitted dose in the initial screening studies to investigate the most suitable input and process parameters to take to an optimization study by employing QbD principles through Design of Experiment. Results revealed the superiority of the nanoparticle aggregates containing DPIs in delivering high emitted dose, high FPF and targeted MMAD. Design space in QbD analysis showed that when using a concentration of API between 4% to 5% w/w accompanying with polymer concentration ranging from 0.5% to 0.8% w/w using sodium alginate or concentration of API is between 2.7% to 4% w/w accompanying with polymer concentration ranging from 1.2% to 2% using sodium alginate will get the desired outcome. Similarly, favorable critical quality attributes (CQA) results were attained with chitosan as a polymer, when API concentration was between 4.5% to 5% w/w and polymer concentration ranging from 0.5% to 0.8% w/w. Therefore, the outcome of this research project could be a starting point for further work to optimize and assess DPI for delivering other drugs employing iron oxide- polymer nano aggregates. |
الأبحاث المستلة |