The biotech industry faces the challenge of how to deliver fragile biomolecules without damaging them. One approach we’re really interested in is using controlled-dose nebulisers to reduce formulation costs and facilitate early-stage efficacy trials. The trials we’ve done have been very successful.
There are lots of reasons why biotech companies use nebulisers during drug development. Nebulisers are less likely to denature proteins and other large molecules, and they avoid the cost of formulation for dry-powder inhalers.
Here at Melbourn Scientific we provide a rapid formulation screening service for poorly soluble drugs. We work with our clients to develop formulations that can be used in first-in-human trials.
A problem with using a traditional jet nebuliser is that the dose is variable depending on the patient’s breathing patterns. This is particularly limiting with drugs that are only effective over a narrow dose range. Also, the heat generated by a jet nebuliser’s 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 of controlled-dose nebulisers to deliver an exact dose.
Controlled-dose 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 allows very accurate dose-range studies which can’t be achieved with jet nebulisers.
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 allow the drug to be delivered as a solution or suspension, which increases the possibilities for formulation. Formulation in solution overcomes some of the challenges of stabilising the drug.
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.
We work with leading-edge device developers and offer a fast formulation screening service. This service will accelerate the development of nebuliser formulations which are increasingly favoured for early-stage evaluation.
Times are changing for drug delivery, and interest in nebulisers is likely to grow. I recently had an interesting conversation with someone involved in the development of controlled-does nebulisers. He is seeing some drug companies looking to bring a drug to market in liquid form for use with a controlled dose inhaler, because drug instability is increasingly common and nebulisers are becoming smaller and easier to use. This saves the time and expense of formulation for dry-powder inhalers.
