The first pMDI was introduced in 1956, followed by the first capsule DPI in 1967. Since then, the variety of drugs delivered via the lungs has grown far beyond those for the treatment of conditions such as asthma and COPD that inhalers were originally designed for. However, these new molecules are often significantly less potent than those for asthma and COPD, and as a result require a greater dosage to achieve the desired therapeutic effect.
Traditionally, due to the tiny quantity of highly potent drug required for a dose, drugs delivered by DPIs are diluted with the inert sugar lactose, commonly referred to as the “carrier fraction” and typically making up at least 95% of the “fill mass”. A typical fill mass (the total mass of formulation filled for a single dose) for the treatment of respiratory illnesses such as asthma and COPD is approximately 10 mg. However, for many new molecules doses can be higher than 50 mg, which exceeds the limit of tolerability for many patients, and presents significant challenges for the current delivery technology, resulting in variability in the delivered dose and an undesirably low respirable fraction.
Our Quattrii™ DPI technology is designed specifically to deal with high masses of low potency drug molecules. Through its unique action, a highly respirable fraction is delivered over the first two seconds of inhalation, making the most effective use of the energy available and providing a consistent and highly respirable dose.
<Above> The brand new Quattrii™ high payload DPI from Cambridge Healthcare Innovations
The current solution to deliver large drug doses to the lung is for patients to take multiple inhalations to reach the required dose. With existing inhaler technology, going beyond one dose presents issues:
Another issue with high dose delivery to the lung is the cough reflex, which may be triggered both by the volume of powder landing in the mouth and throat and the rate with which it is delivered. While coughing is an important airway defence mechanism, it has obvious adverse effects on drug delivery, and so the formulation and drug delivery mechanism should be designed to avoid triggering it. However, existing inhalers deliver the bulk of the dose in a relatively short timeframe towards the beginning of the inhalation. This high flux of powder loading, combined with the high volume of powder for high dose delivery, can induce a cough in the patient.
Our Quattrii™ technology overcomes the above high-mass delivery challenges by:
Existing DPIs were never designed to cope with such high masses of powder. Most inhaler devices today are designed to deliver limited amounts of formulation (between 3-25 mg) per dose:
Modification of these existing technologies to enable a larger dose of a new formulation is likely to require significant redesign, retooling and revalidation of the devices.
It must also be noted that the deagglomeration and aerosolisation mechanisms in devices initially designed for low powder volumes may be wholly unsuitable for high volume delivery, resulting in a drop-off in performance and drug wastage. If your molecule is a biologic, it may be extremely expensive to produce, so any form of wastage is highly undesirable – whether it’s lost in the mouth and throat, or the upper airways of the patient, or retained within the primary container of the inhaler device.
For early-stage exploration of dry powder delivery, a typical “go-to” device is an existing capsule dry powder inhaler (cDPI), such as the Berry RS01. These are designed to work with the industry-standard size 2 and 3 capsules. cDPIs achieve deagglomeration and aerosolisation of the powder by spinning, rattling, or agitating the capsule itself. They can handle a range of dose sizes, however if increasing the size of the capsule is necessary for a high-volume, low potency drug, the whole inhaler is likely to require redesign.
The Quattrii™ DPI technology has been designed to overcome this problem. Scaling the dose up or down, according to the requirements of upcoming new molecules, only necessitates a change to our primary pack – the blister – without changing any other aspect of the device. The Quattrii™ technology works with a range of blister sizes – and each blister size can handle a range of fill masses.
Another issue with cDPIs is that the drug’s primary packaging – the capsule – offers zero moisture protection, meaning hygroscopic formulations need to be packaged in secondary (moisture-proof) containers to achieve adequate shelf life.
Quattrii™ avoids this complexity by using a coldform blister as the primary pack, removing the requirement for secondary packaging, providing inherent moisture protection right up to the moment of use and significantly improving usability.
<Left> 100 mg of powder in a size 3 capsule (left) and in a Quattrii™ blister (right, lid foil removed). The Quattrii™ blister can be larger or smaller, depending on the dosage requirements.
Ultimately, our ethos is to improve the lives of patients through the superior delivery of drugs, enabling better management of respiratory conditions, whilst minimising patient side-effects and drug wastage. Book a meeting with us here to find out how our Quattrii™ technology can help delivery your drug.