Using the lungs as the delivery point for drugs is not a new development, particularly in regard to products designed to combat conditions in the lungs themselves. However, innovations are still being managed in the area, with Insmed becoming the first company to be able to deliver the antibiotic, amikacin, via inhalation.
Work is also ongoing to find new methods of delivery, such as research looking to harness microjets that naturally occur in fruits.
One existing form of delivery, capsule-based inhalation, is of growing interest to the industry, according to research carried out by Fernando Diez, scientific business development manager at ACG.
Diez recently published research that suggested the number of papers reporting test results on capsule-based inhalers had more than doubled between the periods 2001-2005 and 2013-2015.
In-PharmaTechnologist (IPT) spoke to Diez (FD), alongside his colleague Justin Kalafat (JK), scientific business development manager at ACG North America, to see where this interest could lead – including applications in oncology and lung infections – and its strengths compared to other forms of inhalation delivery.
IPT: What are the benefits of capsule-based inhalers?
JK: When you look at capsule-based inhalers, and dry powder inhalers in general, when you compare those to the other common types of inhalation, such as nebulisers and meter-dosed inhalers, the dry powder inhaler is very simple to use and doesn't require the use of a propellant.
Meter-dosed inhalers, formulated in a solution or suspension with a liquid, have to use a propellant whilst also requiring coordination between the actuation of the device and the inhalation itself. When you look at the nebuliser, you're transforming the liquid into an aerosol and there's also a coordination between the device itself and the patient.
If you look at the capsule-based inhalers, they're basically a lot simpler to use and a lot more efficient, which is one of the reasons they're becoming more and more common for some of the new therapeutic developments.
IPT: With capsule-based inhalers being easier to use, is there a suggestion they may aid in patient adherence?
FD: We don't have any quantitative data, but if we define adherence as the degree to which patients follow their doctor's advice, we can see that there is a correlation between adherence and the simplicity of use of any device. As Justin mentioned, capsule-based inhalers are very easy to use and the mechanism is very logical – the only thing you have to do is take the capsule from the blister and place it in the device then inhale.
IPT: Has there been a marked increase of interest in this form of delivery from industry?
JK: What we're seeing, in the last two years, is there is a lot of development activity going on, particularly in the US and Europe. Traditionally legacy products are in the areas of chronic obstructive pulmonary diseases and asthma. What we're seeing now is a lot of companies working on other types of drugs to treat pulmonary hypertension, lung infections and oncology drugs. There are a lot of different reasons, for instance, if you consider inhalation in oncology, it's a simpler process over other forms delivery, such as intravenously.
The other thing we're noticing is that a lot of the commercialisation aspects of these legacy products are done in Europe but we're seeing a lot of the developments, working on inhalation, shifting across to the US. We have a commercial estimate of around 10 billion capsules per year, in the US, but there's a lot of new indications [that may add to this] potentially, as folks look to develop generic products and also these niche products I mentioned.
IPT: Is there a cost benefit of this type of delivery?
JK: There is. When you're looking at cost, specifically when you're looking to other types of inhalers, the capsule-based inhaler only has between 6-10 parts but, if you're looking at some of the other devices, you may have somewhere up to 20 individual parts.
The other side is that it is easier and more cost-effective at manufacturing to fill a capsule than to fill a blister or reservoir for the other types of inhalers.
IPT: From a manufacturing standpoint, is it a more complicated process producing the capsules?
FD: The manufacturing is the same, the only difference is the composition of the capsules. In a standard capsule, the most important point is the solution. In capsule-based inhalation, the capsules must be open and the powder inside must be delivered in an easy way.
This is why the polymer used for making these types of capsules is very important and are different compared to standard capsules. They are different, in terms of molecular weight, and the internal surface of the capsule. It is very important that the powder leaves the capsule very easily, with no sticking, and so we use an internal lubricant.
IPT: What other advantages does this form of delivery hold?
FD: Capsule-based inhalers belong to the category of dry powder inhalers, which do not use propellant whereas metered-dose inhalers do. The propellants consist of greenhouse gases, which are not very environmentally friendly. If we consider the carbon footprint, dry powder inhalers have a footprint between 14-16 times lower than metered-dose inhalers.
IPT: What innovations are occurring within the area?
FD: A new device was developed recently, which included new electronic technology – added to increase adherence. The company, Novartis, made use of the acoustic signal – the acoustic signal of a successful inhalation event is completely different from the unsuccessful event. It is possible to transform this into a digital signal and therefore track the events. The doctor can then measure the adherence to the treatment and take some corrective actions.
Fernando Diez is the scientific business development manager at ACG. Diez’s work mission is creating new business opportunities outside of the formal review/tender process. Diez has an MBA and degree in chemistry, and has published several papers on capsule technology.
Justin Kalafat is a scientific business development manager at ACG North America, collaborating with the pharmaceutical and dietary supplement industries across North America on expanding ACG's capsule market share. Prior to joining ACG in 2014, his background includes degrees in chemistry and roles within the generic pharmaceutical industry in quality control and procurement.