CHARACTERIZATIONS OF A NEW DRY POWDER INHALER (DPI) FOR PULMONARY DRUG DELIVERY

Pulmonary drug delivery, as one of the most common alternative administration routes for injection, has been widely developed to perform effective local (e.g. asthma and chronic obstructive pulmonary disease) or systemic (proteins and peptides) therapy purpose. During this administration procedure, the therapy effects depend on many key factors, including fine powder properties, formulation of the drug powder, design of the dry powder inhaler, and operation of patients and so on. Especially, the mechanical structure of the dry powder inhaler plays the most important role, for example, the loading and emission consistency, air flow resistance, residue of fine drug powder, de-agglomeration construction, and the principle of generation of the powder aerosol and so on. In this research, based on previous fundamental study on an old dry powder inhaler, a new dry powder inhaler has been developed and characterized. Different fine drug powder formulations were prepared to investigate the enhanced performance of the new dry powder inhaler. Several experiments, such as dose uniformity, emission consistency and in vitro particle deposition and distribution test, have been conducted to evaluate the new device. All the above test results were considered as the guide to modify and redesign the new dry powder inhaler. As an attempt, the puncture diameter of the new dry powder inhaler was increased, and the effects on the drug delivery performance were also evaluated. In addition to the consideration of device design, studies on the formulation development have been carried out in this research. The effects of lactose with different particle size were compared as the carrier for the dry powder formulations. The drug formulations were prepared by different methods, using coffee grinder or rotary blender, in order to optimize the production process. The effects of different amounts of carrier and stability test for the storage of formulation have been conducted. This thesis successfully developed a new dry powder inhaler and discovered proper drug formulation for this device. With drug formulations using large lactose as carrier, the new DPI showed a good drug delivery performance with high consistency. Also a filling by hand process and a filling machine were developed and proved to be qualified for the application to dry powder inhaler