Prosonix has announced the publication of a new review paper describing how its novel particle-engineering-led approach to respiratory medicines is enabling the development of ‘smart’ excipient-free, drug-only Multi-component Particles™ (MCPs™) that offer the potential of more effective inhaled combination therapies.
Since their introduction, inhaled combination therapies have improved the management of major respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
There is compelling evidence that combination therapies acts synergistically to reduce inflammation and constriction of the airways, preventing disease progression, providing symptomatic relief and improving quality of life by providing treatment for complications and exacerbations.
Drug combinations form the basis of several blockbuster respiratory medicines such as GlaxoSmithKline’s Advair®/Seretide® and AstraZeneca’s Symbicort®.
Both of these products are based on combinations of an inhaled corticosteroid (ICS) plus a long-acting beta-agonist (LABA).
Combinations of a LABA with a long-acting muscarinic antagonist (LAMA) and triple ICS/LABA/LAMA combinations are also being developed.
In the new review, published in the Spring 2012 issue of European Respiratory Disease (ref. 1), the authors highlight the advantages of combining two or more active pharmaceutical ingredients (APIs) in exact and consistent ratios in a single, excipient-free, drug-only particle (known as Multi-component Particles or MCPs) compared with mixed powder formulations.
This is particularly beneficial when there is a synergistic action between the APIs, which ideally should be delivered and deposited together at the targeted site of action in the lung.
Going into more depth, the authors describe the use of Prosonix’ unique ultrasonic particle engineering approach to creating MCPs comprising equivalent ratios of fluticasone propionate (FP) and salmeterol xinafoate (SX) as in Advair®/Seretide®, and of budesonide (BDS) and formoterol fumarate dehydrate (FFD) as in Symbicort®.
These MCPs were found to retain the ratio of APIs of the Originator products in both formulation and delivered dose via pMDI.
Co-association of respiratory APIs in the form of MCPs was consistent throughout the process chain of manufacturing, formulation and delivered dose, offering the promise of achieving true synergy, optimal therapeutic efficacy and reduced dosing.
In developing respiratory MCPs, Prosonix believes it is overcoming the main challenge faced by the companies developing combination products of maintaining consistent ratio of the APIs during formulation and upon re-dispersion and deposition in the lung.
The excipient-free, drug-only nature of the MCPs is particularly advantageous. The majority of combination products on the market and in development are based on dry powder ‘blends’ of APIs, which once aerosolized and inhaled are co-deposited randomly and therefore reduce the opportunity for a synergistic effect.
Furthermore, current manufacturing methods - primarily jet milling large particles into smaller particles - change the chemical and physical stability of the particles. As a result, this creates little, if any, co-association among the actives.
David Hipkiss, Prosonix’ CEO, said: “The treatment of respiratory disease remains a high unmet need, despite the recent development of new therapies. The effective production and delivery of combination medicines in a consistent, stable and co-localized manner are lacking, given inefficiencies in current manufacturing and formulation processes. This paper highlights the potential for our engineered excipient-free, drug-only Multi-component Particles to deliver more effective and better tolerated respiratory medicines for patients.”