تاريخ مجلس الدراسات العليا

2021-06-23

اسم الطالب

نور رضوان فخرالدين اشقر

ملخص الرسالة

The prevalence rate of respiratory disease is escalating globally, which represents a severe danger to human health, an economic and social burden. Novel strategies for the management of respiratory conditions have been developed including the use of targeted inhaled Fixed Dose Combination (FDC), nanomaterials and dry powder inhalers (DPI). FDCs incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcome. However, development of dry powder inhalers, particularly for FDC, encountered several challenges pertinent to formulation uniformity and reproducibility. Therefore, the aim of this project was to employ nanotechnology and develop a FDC of DPI for a market-leading active pharmaceutical ingredients (fluticasone propionate (FP) and salmeterol xinafoate (SAL)) for the treatment of asthma. Nanoaggregates were prepared using a biocompatible and biodegradable polyamide based on the amino acid tyrosine as basic component using interfacial polymerization process. The process entailed polymerization and encapsulation in a one-step (FP/SAL- Try-PA NPs) giving advantages of practicality and effectiveness. The produced tyrosine polyamide drug loaded nanoparticles were developed and evaluated using various techniques including content uniformity, particle size, FTIR, TEM, DSC, XRD and aerodynamic performance among others. The optimized formulation demonstrated high entrapment efficiency for the two actives that exceeded 90%. The aerodynamic performance in terms of emitted dose and Fine particle fraction and respirable dose were superior to the marketed product (Seretide Diskus®). The prepared nanoaggregates were able to disperse upon deposition in the lower parts of the respiratory system allowing for maximum benefit of the nanoparticles (using particle size analysis). The in-vivo studies showed that the FP and SAL reached the lungs of mice in a reproducible manner. The final formula showed an extended drug release profile with nanoaggregates using polyamides based on Tyrosine and interfacial polycondensation. This would provide specific benefits and advantages which are considered as a promising new research field.