A new inhalation device uses an innovative mechanism to ensure that patients receive the correct drug dosage every time.
Most people are familiar with metered-dose inhalers. Commonly used by asthmatics, they deliver a specific amount of medication to the lungs in the form of a short burst of aerosolised medicine that is inhaled by a patient.
But while such devices are the most commonly used delivery system for treating respiratory diseases, they rely on a user to co-ordinate the firing of the device with an intake of breath, a procedure that, if not optimised, can lead to complications in delivering the correct dosage of drug to the lung.
Dry-powder inhalers, on the other hand, do not suffer from the same synchronisation issues as they rely on the force of a patient’s inhalation to extract a drug from the device. During the inhalation process, the dry-powder inhaler breaks the active drug ingredient away from a carrier, such as lactose, into fine aerosol particles that are small enough to reach the lungs.
Because there is an intrinsic relationship between an inhaler and the drug formulation used inside it, each inhaler must be designed specifically to optimise the amount of a drug that it delivers. So when Sun Pharmaceuticals, an Indian maker of speciality pharmaceuticals and active pharmaceutical ingredients, was looking to bring a new inhaler to market it turned to Cambridge Consultants to help develop it.
Commercial director Phil Lever explained that the engineering team at Cambridge Consultants was well aware of the importance of ensuring the inhaler would deliver the drug only once a patient had achieved a sufficient inhalation flow rate. That would ensure that complete de-agglomeration of the drug formulation or separation of the drug from the carrier would occur and that the required dose would enter the lungs at the specific particle size that was demanded.
With this aim, the team developed a bespoke mechanical breath-activation mechanism (BAM), a mechanical valve-like subassembly, which ensured that only when the patient’s inhalation rate reached a predefined value would one of the 60 blister packs containing the drug and carrier be punctured, the powder aerosolised and the drug delivered to the patient.
Besides ensuring the device only triggered once the correct airflow had been achieved, the engineers also designed the chamber through which the formulation passes on its way from the blister pack and out of the inhaler to ensure that the de-agglomeration process would be as effective as possible.
To do so, they performed extensive mathematical modelling of the airflow through the chamber, optimising its geometry to ensure that, once the user inhaled, it would result in an airflow turbulent enough to ensure the drug would separate from the lactose carrier particles through colliding both with one another as well as the sidewalls of the chamber. With modelling completed, they developed a rapid prototype model of the inhaler that was tested using an Andersen Cascade Impactor that ensured they had achieved the desired particle-size distribution of the drug released from it.
The device is capable of delivering significantly more drug to the deep lung than conventional products
While the device is capable of delivering significantly more drug to the deep lung than conventional products, Lever was reluctant to disclose specifically how much more for confidentiality reasons. However, he could say that the inhaler is capable of producing more than 40 per cent fine-particle fraction. This is a measure of the proportion of the dose delivered by the device that is potentially available to the lung and can be correlated with the amount of drug that actually reaches the lung.
In practice, optimising the amount of drug that can be inhaled means that the remaining portion of the drug that is delivered in the mouth or to the back of the throat is dramatically reduced, meaning that 50 per cent less of the active drug is required to be preloaded into the device in comparison to a standard inhaler.
Additional user-friendly design features include a mandatory FDA-required numerical dose counter, to enable a user to see how many more doses are left in the inhaler before it runs out; a luminous feature, to make the device easier to find during the night; and a small pop-out Braille button, to alert blind or partially sighted users that there are only a few doses remaining.
The patented drug-separation mechanism has now completed clinical trials and Cambridge Consultants is working with Sun Pharmaceuticals to ready the device for manufacture.