Controlled-Dose Nebulizers Show Potential for Early-Stage Drug Development

As proteins and peptides become increasingly common as inhaled drugs, the biotech industry faces the challenge of how to deliver these fragile biomolecules without damaging them. New study trials have shown that controlled-dose nebulizers might reduce formulation costs and facilitate early-stage efficacy trials.

Nebulizers are frequently 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 (Melbourne, UK) has developed 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, a formulation scientist from Melbourn Scientific, stated, "A drug which is only effective over a narrow dose range poses problems when used with a traditional jet nebulizer, 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 nebulizers to administer an exact dose. These nebulizers 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.”

While controlled-dose nebulizers are more expensive than jet nebulizers are 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. Therefore, for small-scale trials they offer significant advantages.

Nebulizers 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. They allow formulation in solution and so overcome some of the challenges of stabilizing the drug. However, fragile active pharmaceutical ingredients (APIs) can be denatured by conventional jet nebulizers. The drug is delivered as an aerosol created by a compressor blowing air through the solution or suspension at high speed. A controlled-dose nebulizer, 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 provides a fast formulation screening service. This service will accelerate the development of nebulizer formulations that are increasingly favored for early-stage evaluation. The company's screening service is supported by recent investment in a new platform technology that will allow analysts to assess a broad range of formulations.

Interest in nebulizers is expected to grow. A spokesperson for one of the controlled-dose nebulizers commented, "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.”

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