Administration of insulin using DPI inhalers

A dry powder Inhaler called „Dreamboat“

MannKind is a biopharmaceutical company which focuses on the development of therapeutic products for the treatment of diabetes and cancer – with technologies that allow pulmonary absorption of drugs. AFREZZA® is a new, fast-acting, inhaled insulin. In about 60 clinical trials involving more than 5,300 volunteers, MannKind was able to show that AFREZZA® can be used to control high blood sugar in adults with type 1 and type 2 diabetes.

After approval by the U.S. Food and Drug Administration in 2014, the drug has been introduced to the market in 2015. The therapeutic system consists of a dry powder inhaler called “Dreamboat” and a powder filled cartridge. This cartridge is inserted into the inhaler for a singledose application, and discarded by the patient after the inhalation process. The inhaler is re-used over a 15 day period. Various amounts of insulin can be dosed using cartridges containing different amounts of powder. The cartridge lids are color coded according to strength, in blue, green and yellow.

The cartridges contain powder particles loaded with insulin. By inhaling the powder, the insulin passes into the bloodstream through the lungs of the patient. MannKind utilizes a Technosphere® powder formulation which is based on an organic molecule called Fumaryl Diketopiperazine (FDKP). The unique features of FDKP is its ability to form Technosphere® particles, its rapid dissolution in the lung and its elimination from the body without undergoing metabolism.

High-precision dosing and 100 percent weight verification

The MannKind Powder Filling and Assembly Machine is based on the Harro Höfliger FLP-200 machine platform (Filling machine, Lengthwise transport, Pallet, 200 mm pitch). In this machine platform, a tray serves as the transport medium. At the end of the machine, after cleaning and complete product removal, the tray is returned to the start of the process.

Vibrating conveyors feed the cartridges and corresponding covers into the line. A Pick-&-Place-system positions each cartridge in the trays. A so-called ‘walking beam’ transports the trays from station to station. Two vacuum drum filler systems provide high-precision dosing of the powder into the cartridges. Every dosing system is equipped with an AMV-sensor (Advanced Mass Verification), for one hundred percent weight verification of the powder dosing. That means the AMV-sensor verifies 400 individual quantities of powder per minute. In the event of under-dosing or over-dosing, the machine sorts out the affected cartridge and moves it to the fail part ejection area.

The filled cartridges are sealed with color-specific lids and subsequently coded with laser markings. Every machine work step is followed by a control step, which checks the previous operation. Correctly filled and fully closed cartridges with the proper colored lid and have received a legible LOT-coding, are moved to the pass part discharge of the machine.

From there, the cartridges are transported into an intermediate storage. From there into a automatic blister machine. Fifteen (3x5) Cartridges per blister are packaged at a time. Already three machines were delivered and are running smoothly. The first machine was used in the production of the required sample quantities during clinical development phase then converted to supply commercial product.