Why should we bother to engineer particles? Formulation performance is more than just about particle size. APIs are in essence performance chemicals and it is size, morphology, surface energy, and critically surface 3D geometry that govern particle performance in inhaled medicines formulation. API particles can be fully engineered via controlled crystallization leading to much simpler drug delivery platforms.

It can be difficult to obtain 1-5 micron crystalline particles by conventional technology. In addition, delivery of drugs via the lungs requires superior particles. Prosonix technologies such as DISCUS^TM and SAX^TM uniquely facilitate control of size, shape, surface geometry, surface free energy, and crystallinity. They are also ideally aligned with the new FDA QbD philosophy.

The lung presents us with an excellent drug delivery route, but with significant manufacturing challenges for the drugs in question. The lung structure is ideal for non-invasive systemic delivery of drugs given the surface area available for absorption, allowing the drugs to easily pass into the bloodstream from the deep lung yielding rapid onset of action; improved efficacy and tolerance. Deep lung delivery for greater systematic availability or local effect in the deep lung requires particles less than 3 micron in size.

The upper respiratory tract is ideal for the treatment of such diseases as asthma and COPD, as well as respiratory infections, requiring particles 1 to 5 micron in size. However many delivery devices are inherently and unnecessarily complicated. Prosonix technologies can deliver superior particles allowing the use of less complex dry powder inhalation (DPI) devices.

So what are the ideal respiratory particle requirements? We need high FPF, ED, dose consistency and uniformity and should be achieved independent of the type of device and inhalation flow rate. These can be achieved by having:

o Correct aerodynamic particle size (mass medium aerodynamic diameter MMAD)

o Right aerodynamic diameter - function of density and dynamic shape factor

o Narrow particle size distribution

o Low aerodynamic dispersion forces to aerosolise

o Good physical and chemical stability – crystallinity, polymorphism

o Low density & large volume diameter for better dispersion & efficient lung delivery

Interestingly, rod-like, needle-like particles and less than spherical -indeed twinned crystals as shown above -might have a better aerodynamic performance by being able to orientate in the air flow and behave like smaller particle.

So how are Dry Powder Inhalation formulations made? The formulation consists of two parts: the drug – micronized or engineered - typically cohesive and ideally 1-5 micron and an inert carrier - generally micronized lactose - used to carry the drug, but much larger at 60 -150 micron. The materials are typically low-shear blended.

In these formulations the surface texture plays a crucial role and has a significant effect on the important cohesive - adhesive balance (CAB) which governs the ease (or difficulty) in the drug particles being released from the carrier particles by the force of inspiration. With Prosonix engineered particles we can carefully control the CAB and in doing so we can develop more useful drug formulations.

Budesonide

We have carried out rigorous in vitro inhalation studies using external partners on Prosonix engineered Budesonide, and inhaled corticosteroid using the NGI (Next Generation Impactor).

The aerosolization efficiency of SAX and DISCUS budesonide has been assessed in binary (with micronized lactose) dry powder inhaler (DPI) formulations. In all cases Prosonix powders were 50-120% more efficient in terms of Fine Particle Dose and certainly superior in terms of emitted dose.

Beta -2-adrenoreceptor agonists - long and short-acting bronchodilators

We have carried out rigorous in vitro inhalation studies using external partners on Prosonix engineered  beta 2-adrenoceptor agonists and bronchodilators, using the NGI (Next Generation Impactor). The aerosolization efficiency of SAX particles has been assessed in binary (with micronized lactose) dry powder inhaler (DPI) formulations. In all cases Prosonix powders were over 50% more efficient in terms of Fine Particle Dose and.

There is also a real drive to produce Combination particles whereby two or more APIs in an exact ratio can be converted to a 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.

For perfect particles for inhalation partner with Prosonix today!