The Development of A New Dry Powder Inhaler

A new dry powder inhaler (DPI) for respiratory drug delivery was developed. This novel device is characterized by a micro-dose, passive delivery and multiple doses individually sealed in one replaceable disk. The micro-dose delivery system uses only a small amount of excipient, such as 2-3mg lactose, thereby improving the drug delivery efficiency. The passive delivery method eliminates the need for coordination between breath and device actuation such as the pressure metered dose inhaler (pMDI). Finally, 14 doses on a disk reduce the need to frequently change dosage disks. In addition, each dose is effectively protected by a blister package to minimize damage from moisture and oxygen. A comprehensive evaluation on key parameters, including dosage emittion, air flow resistance and fine particle fraction, has been conducted. The air resistance of our device is about 0.06 kPa0.5·min/liter, slightly higher than several marketed products but close to Inhalator®. The in vtiro performance results show that this new dry powder inhaler is able to achieve a high efficiency for drug delivery, with 10% of drug remaining in the device. This device can also effectively disperse drug particles to acquire a high fine particle fraction (FPF) as 50%. A primary stability research demonstrates that the FPF of a formulation containing 5%-fine additive would stay at 40% when being accelerated for 3 months. Furthermore, comparative studies between this novel inhaler and typical marketed products –such as Diskus®, Turbuhaler® and Aerolizer®, show that when combined with suitable formulations, the FPF of our device could be about 25% as Diskus® and Aerolizer®, or above 40% as Turbuhaler® and Clickhaler®. When using the same powder, our device shows a FPF of 50%, similar as Clickhaler® and Aerolizer® and higher than Twister®, indicating similar or better performance of our inhaler device to disperse drug particles. Because no existing powder filling system could satisfy the filling requirements of this new inhaler, a new powder dispensing and packaging system was developed. The new powder filling system designed and implemented in our lab was evaluated and optimized to improve the uniformity of filling weight and drug content among disks/blisters. The relative standard deviation (RSD) of filling weight among disks and blisters is 1~3% and 6~8% respectively. The uniformity of drug content among disks, with a RSD from 2~5%, demonstrate the filling system could completely meet the requirements of the inhaler development. Suitable drug formulations for this new DPI were also developed, including research and optimization of powder composition and processing. The preparation of a uniform drug-lactose blend was investigated, including the mixing method, mixing time & speed, and mixing sequence. The composition studies are conducted to better understand the effect of the drug particle and excipient on the drug delivery. Experiments show that the powder composition and processing have a significant influence on the in vitro performance, which can be controlled and adjusted to obtain the desired results. For example, when increasing the ratio of fine additive from 0% to 20%, the FPF is increased from 20% to 45%. Meanwhile, if the mixing time is extended from 2min to 10min, the FPF experiences a drop from 35% to 22%. With the optimization of powder composition and processing, development of the powder filling system and implement of the new inhaler device, this novel inhaler can deliver 2-3mg powder per dose with an adjustable fine particle fraction from 25%-50%