Development of microparticular DRY powder inhaler formulations of vancomycin for pulmonary delivery

The aim of this study was to prepare vancomycin hydrochloride microparticles that have aerodynamic properties, high drug encapsulation efficiency and can release for 24 hours for local administration to the lungs and investigate the distribution of the drug in the lungs with the help of in vitro performance tests. Especially in lung infections, systemically high amounts of antibiotics should be administered to achieve the required minimum inhibition concentration in the essential area. This brings systemic side effects with it. Considering that the lungs have advantages such as large surface area, thin epithelial layer, high vascularity network and elimination of first pass effect and it is aimed to prepare a microparticular dry powder formulation of vancomycin hydrochloride. Microparticular dry powder formulations were prepared by the W/O/W emulsion solvent evaporation technique. In the preparation of the formulations, PLGA (poly (lactic-co-glycolic) acid), which has been approved by the FDA to be biocompatible and degradable was used. Porosity forming agents have been added to the formulations to control release and improve aerodynamics. After that particle size and particle size distribution, zeta potential, encapsulation efficiency, product yield and in vitro release studies were investigated in microparticle formulations of the added porojen. Based on from results the ABC-7,5 formulation was found suitable and in vitro performance tests were continued with this formulation. The aerodynamic properties of the microparticles were investigated by mixing the selected formulation with the lactose available in the market (InhaLac® 230, Lactohale® 200, Respitose® ml003, Respitose® sv003) with the help of NGI and DUSA tests. The excipients used have been found to improve the aerodynamic properties of the microparticle formulations. The results of our thesis concluded that the microparticular dry powder formulation of vancomycin hydrochloride was prepared with appropriate properties. Key Words: vancomycin, dry powder inhalers, microparticles, NGI, DUSA