The Prosonix power ultrasound assisted particle engineering technology UMAX®, (Ultrasound Mediated Amorphous to Crystalline transition) can be used for the manufacture of optimal particles designed and formulated as inhalable drug products for respiratory disorders. UMAX facilitates the manufacture of both spheroidal and more regular shaped particles for Dry Powder Inhalation (DPI) or pressurized Metered Dose Inhalation (pMDI). Particles for inhaled medicines can be manufactured with the optimal performance attributes of size, shape, surface rugosity, low surface free energy, crystallinity and stability.
In all cases respiratory doses and fine particle fraction (FPF) can be improved significantly and often by over 100 % when compared with mechanically micronized material. Inhalable pharmaceutical materials can now be manufactured with superior clinical performance and improved patient compliance, regardless of the device used to deliver the actual drug substance. UMAX can be used to manufacture inhaled combination particles whereby two or more pharmaceutical ingredients can be processed into highly crystalline particles. This is particularly beneficial when there is a synergistic action between the multiple drugs, requiring them to be delivered together.
Size reduction (or ‘top-down' destructive) methods for mesoscopic particles, such as fluid energy milling (or 
micronizing), are capable of achieving the target size range, but the high energy required for such processes often damages the crystal surface, leading to highly charged and cohesive particles which results in the chemical and physical instability of the drug. We may also see undesirable surface polymorphological transformation and amorphous structure. Micronization can also lead to generation of considerable heat which may be incompatible with the material of interest.
UMAX particle engineering technology for the production of microcrystalline particles with narrow size distribution can be used to manufacture particulate pharmaceuticals with defined physicochemical properties. The technology is now being used to manufacture multi-kgs powders suitable for use in structured drug products for asthma and COPD.
The UMAX particle engineering technology can be used for increasing the crystallinity of at least one solid material which is less than 100% crystalline comprising the process steps of contacting the solid material with solvent in which it is insoluble and applying ultrasound in order to convert the amorphous, semi-amorphous or semi-crystalline material into highly crystalline particles, quite often with some retention of particle morphology. The pharmaceutical material with reduced crystallinity can be prepared by any number of means including spray drying (being the preferred method for spheroidal particles), lyophilization, micronization, and rapid precipitation.
The UMAX processing of the product via spray drying is divided into 3 distinct stages as shown:
- 1. Spray drying of API dissolved in an appropriate solvent to form a dry API powder of the correct particle size distribution.
- 2. Ultrasonic processing of the API loaded into a non-solvent liquid to form a slurry.
- 3. Final isolation (either by spray drying or supercritical CO2 processing) to produce a final batch of dry API powder.
Our proprietary screening methods for UMAX and related techniques involve Design of Experiments taking account of: solvent and solubility, precise spray drying conditions, productivity and flow rate, temperature, and ultrasound and non-solvent .
The UMAX ‘solution to particle' methodology avoids many of the issues assocaited with the various methods available to date. Importantly, the use of UMAX also allows the production of uniform and often spherical drug particles with unique nanotopology and superior aerodynamic properties. UMAX has been applied to many compounds to date including over 50 steroidal asthma drugs, long-acting beta-agonists (LABAs), long-acting muscarinic agonists (LAMAs), antibiotics for inhalation or oral delivery, and many new chemical entities (NCEs) under development.
UMAX also provides the platform for a novel particle engineering solution whereby a single droplet containing the two or more APIs in an exact ratio can be converted to a combination particle containing the very same drug substances as separate crystalline entities. In combination therapies for asthma and COPD the APIs often have synergistic action at molecular and cellular level (such as inhaled steroids and long-acting beta agonists) and need to be delivered in an exact ratio to the site of action in the lung. Indeed triple therapy has now also become possible with UMAX technology.
Particle engineering techniques such as UMAX, involving the creative use of ultrasound, can be used to engineer microcrystalline particles for both DPI and pMDI, in turn yielding structured drug products that can out-perform quite significantly the existing commercial products. In addition to superior performance, in terms of in vitro lung deposition and FPF, the products and particles show greater medium to long term stability over micronized material.
Prosonix has every confidence in UMAX becoming a worldwide manufacturing technology for both inhaled and oral (where particle size is important) medicines. UMAX is now available for partnering and evaluation.
