CombiSphere™

Smart respiratory combination particles

Combination inhalation therapy (e.g. a LABA and an ICS) provides convenience to the patient along with synergistic pharmacological actions, leading to better compliance and therapeutic outcomes. Conventional blending of the active pharmaceutical ingredients (APIs) with lactose carrier particles is commonly used in formulating combination inhalation products. However, the blend performance is highly variable, depending on the amount of amount of fines, surface roughness, API polymorphic form, production batch and grade of the carrier lactose. Furthermore, unpredictable or preferential adhesion of one API over the other on the lactose, along with self-agglomeration of one or both drugs, will cause content segregation and dose non-uniformity. Any difference in the particle properties between the APIs, as manifested in different interactions between the drugs, carrier and container surface, may lead to changes in the fine particle  fraction (FPF), device retention and dose variability.

To address these issues, Kuecept Ltd has developed a robust and scaleable particle engineering technology (CombiSphere™) which enables the rapid manufacture of crystalline drug combination particles suitable for delivery by both carried-based DPIs and suspension based pMDIs.

Each particle produced by the CombiSphere™ technology contains two or more actives in an exact ratio and which consistently demonstrate improved Fine Particle Dose (FPD) and co-deposition delivery compared to using individual micronized powders.

Key benefits:

• Particle production independent of the chemistry of the actives, allowing a wide range of formulations to be manufactured
• Ability to rapidly manufacture batches from mg to multi-kilo scale using robust and  scalable processes
• Particles demonstrate ideal physico-chemical properties for secondary processing, i.e. flow, surface charge, cohesion / adhesion forces
• Particles are highly crystalline in nature, ensuring physical stability of material during processing and storage (quarantine)
• Particles remain stable during high-shear blending (i.e. no particle fracture) ensuring consistent dose content uniformity
• Ability to formulate particles into drug only pMDIs and carrier based DPIs

CombiSphere™ is available for evaluation for specific drug product manufacture and testing. In addition, Kuecept have developed the following combination products which are available for evaluation and licensing:

• Fluticasone/salmeterol (250mcg/50mcg). Available as DPI and pMDI
• Budesonide/formoterol (160mcg/4.5mcg and 80mcg/4.5mcg). Available as DPI
• Ipratropium bromide and albuterol sulfate (21mcg/120mcg). Available as pMDI