Summary

The study aims were to demonstrate that spray drying technology can deliver the same dose of drug substance in a combination therapy formulation as from the equivalent monotherapy formulations. Salbutamol Sulphate (SS, a Bronchodilator) and Ipratropium Bromide (IprBr, a muscarinic agent) were used as model drug substances for this work; they are known respiratory drugs with complimentary modes of action and both are water-soluble supporting the spray drying approach. 

This spray drying technology enables formulations, which can be consistently produced with a narrow particle size distribution, uniform in drug content, morphology and surface chemistry enabling consistent delivery. This technology also gives the ability to increase the drug content or alter the ratios of drug substances within a combination formulation whilst maintaining particle size and surface chemistry so enabling comparable delivery regardless of drug content.  This is important given the regulatory requirement for dose linearity and clinical equivalence between monotherapies and their respective combination therapies.

The study was successful in meeting its aims, each drug substance showed a consistent %FPF taken from the impactor sized mass (ISM) which included NGI stages 2-MOC. The data demonstrated that an increase in API concentration by five times did not influence aerosol performance. Assessment of aerodynamic performance showed that the drug mass deposition across the NGI was consistent for each drug substance independently of being mono or combination formulations

Key Message

Spray drying technology enables monotherapy to combination therapy in-vitro equivalence for fixed dose DPI delivery to the lungs. This is an enabling technology where monotherapy and combination therapy formulations are required as it supports the development of formulations with dose linearity, and can enable clinical equivalence between therapies.