Dry Powder Inhalation (DPI) is the most common form of inhaled treatment for diseases such as asthma, COPD, bronchitis and emphysema. Patients use a device called a dry powder inhaler to deliver the appropriate dosage of an Active Pharmaceutical Ingredient (API) into the patient lungs.
These inhalation devices contain a powder mixture that is under pressure. There are three main components of the powder mixture, the API, a carrier which is typically lactose and additives such as Magnesium Stearate and Lecithin for material flow control, etc. Generally API’s are cohesive and amorphous.
The API particle size distribution is generally between 1 to 5 microns. As such, the API is dependent on a carrier with a much larger particle size distribution to carry the API from the inhaler into the mouth of the patient. The API is released from the carrier and released into the patient’s lungs while the carrier stays in the patient’s throat and goes into the stomach. The carrier particle size distribution is generally between 40 to 200 microns. The API is a very small percentage (<2%) of the entire mixture with the carrier about 90%. The rest are additives.
Jet Mills (Spiral Jet Mills (AS) or Fluidized Opposed Bed Jet Mills (AFG) are generally used to mill the API down to the appropriate particle size distribution. The Spiral Jet Mill is the most commonly used type of Jet Mill to micronize the API. This mill is preferred, due to its simple design, with no moving parts in the mill, its accessibility for cleaning and inspection. This mill can also be designed with CIP/SIP options. (Note: Other methods can be used to achieve the appropriate particle size distribution for API such as crystallization and spray drying.)
The Fluidized Bed Opposed Jet Mill can also be used for API micronization. It is typically selected over the Spiral Jet Mill, if a tight and steep particle size distribution is required. This is achieved using the AFG internal dynamic classifier. Changes to the particle size distribution are also easier with the AFG Mill. The AFG Mill can be designed with CIP/SIP options and explosion containment. The AFG Mill is able to micronize heat sensitive or sticky materials. Comparing to the AS Mill the AFG Mil can be fed with a larger feed size. Both types of Jet Mills can be designed inside of an isolator for OEL Containment Levels <1 µg/m3, 8 hrs. TWA.
A wide variety of milling technologies can be used to micronize the carriers/excipients/additives which are much coarser than the API’s. The typical milling technologies used are: the Fluidized Bed Opposed Jet Mill (AFG), Air Classifier Mill (ACM) and Universal Mills (UMP and UPZ) which are mechanical impact mills. The UMP and UPZ Mills are used mainly as Pin Mills or Hammer and Screen Mills. The Universal Mills have other rotor assemblies for coarser grinds.
After the various DPI components are micronized they are then mixed in a Cyclomix , which is a High Shear/High Speed mixer to coat the API onto the excipients and to achieve a homogeneous mixture. The Cyclomix is preferred, due to the high energy that is imparted to the cohesive powder mixture.
Hosokawa’s milling and mixing technologies range from lab scale (approximately 1 gram for milling and 0.1 L for mixing) to production size equipment. All equipment is scalable from lab scale to production scale.