Nebulisers are often chosen as a delivery mechanism during biotech drug development. They are less likely to denature proteins and other large molecules and they avoid the cost associated with formulation for dry-powder inhalers.
Contract analysis and formulation company Melbourn Scientific provides a rapid formulation screening service for poorly soluble drugs and has been working with its clients to develop formulations that can be used in first-in-human trials.
David Ward, Formulation Scientist at Melbourn Scientific, says: 'A drug which is only effective over a narrow dose range poses problems when used with a traditional jet nebuliser, because the dose is highly variable depending on the patient’s breathing patterns. Additionally, the heat generated by the motor can affect the droplet size.
'In early-stage development the drug needs to be accurately delivered, so for some of the most fragile compounds we have been trialing the use a controlled-dose nebulisers to administer an exact dose.
'These nebulisers only deliver a drug during the first 80% of the in-breath, the time over which the drug is deposited in the lungs. This can be extremely valuable for accurate dose-range studies.'
Although controlled-dose nebulisers are more expensive than jet nebulisers and may require the supervision of a clinician, they have the added advantage that the quantity of drug received by the patient can be accurately controlled and measured. So for small scale trials they offer considerable advantages.
Nebulisers create a mist of medicine that can be inhaled passively, and the drug can be delivered as a solution or suspension, which increases the possibilities for formulation.
Nebulisers allow formulation in solution and so overcome some of the challenges of stablising the drug. However, fragile APIs can be denatured by traditional jet nebulisers. The drug is delivered as an aerosol created by a compressor blowing air through the solution or suspension at high speed. A controlled-dose nebuliser, in contrast, uses vibrating mesh technology which is much gentler and so less likely to damage the drug.
Melbourn Scientific works with leading-edge device developers and offers a fast formulation screening service. This service will accelerate the development of nebuliser formulations which are increasingly favoured for early-stage evaluation.'
Melbourn Scientific’s screening service is supported by recent investment in a new platform technology that will allow analysts to evaluate rapidly a wide range of formulations.
Interest in nebulisers is expected to grow. A spokesperson for one of the controlled dose nebulisers comments: 'Drug instability is increasingly common so we are seeing some drug companies looking to bring a drug to market in liquid form for use with a controlled dose inhaler. This saves the time and expense of formulation for dry-powder inhalers.'
