Orally inhaled and nasal drug products (OINDPs) are a class of therapeutics that have long been used for many years in the treatment of various diseases, particularly respiratory conditions like COPD or asthma.
Since the COVID-19 pandemic, there has been a surge of interest in these handy products, as patients increasingly seek user-friendly alternatives that enable self-administration. Although the simplicity of taking OINDPs for patients cannot be denied, the same cannot be said for their development. For years, drug designers have faced significant difficulties when trying to create products that fulfil the holy trifecta: efficacy, safety and reproducibility.
To get to know the challenges drug designers face in development, how these hurdles can be overcome and to find out more about the latest developments in the field, Annabel Kartal-Allen spoke to Frank Chambers, an OINDP specialist and the Director of Inhalytic.
Wide applications
The development of oral and nasally administered drugs has skyrocketed in popularity over recent years, Frank explains: “There’s been more interest in this area recently because the options are so extensive for this branch of medicine.”
“One of the advantages of inhaled therapy is that you can avoid first pass metabolism in the liver, resulting in a much faster onset of action. It's also a great option for treating neurological disorders, as these drug types can often surpass the blood brain
barrier; improving both onset speed and reducing the dose required for efficacy. OINDPs have also shown efficacy in medication-resistant depression, Parkinson’s and for the treatment of postpartum bleeding.”
The ingredients will not only interact with each other, but with the device too ... these factors are significant obstacles to developers
Industry challenges
With expanding potential present in the OINDP space, researchers are increasing their investments into development. Unfortunately, this isn’t without its challenges. Frank elaborates:
“OINDPs are tricky devices to master, often with complex device formulation interactions. When looking at standard oral presentations, you only need to concentrate on optimising stability, delivery and bioavailability. However, when developing an OINDP, there's always an extra level of intricacy. The ingredients will not only interact with each other, but with the device too. These factors are significant obstacles to developers, so the need for meticulous attention to detail to ensure efficacy throughout development and manufacturing is crucial.”
He continues: “A formulation that’s suitable for one device could be completely incompatible with another — it’s not one size fits all. Optimising your preparation to the type of device you’re using is really important.” Frank also highlights the regulatory processes that all OINDPs must undergo to receive approval: “You need to ensure the product is easy to use for consumers, as well as being
able to satisfy regulatory compliance in terms of stability, performance, quality and reproducibility. The aerosol needs to be highly consistent in particle size, so it can consistently access the site of action.”
Who is Inhalytic?
Inhalytic is an analytical chemistry testing consultancy specialising in the early-stage development of OINDPs and is currently set up like a small university research lab operating in the commercial business environment. The company is based at Discovery Park, an international centre for science and innovation, in Kent. “We generally focus on working with
companies and innovators that have the courage to challenge the norm." Frank states. 
Frank Chambers, an OINDP specialist and the Director of Inhalytic
Future industry developments
Although there has been significant progress in the field of oral and nasal products, there’s still so much more scope for expansion in the industry, Frank comments: “Most recent advances in vaccine technology has led to an increase in interest in development of
complex biologic agents for administration via inhaled route. This has been particularly reflected by a significant increase in an interest in development of compounds for nasal administration and soft mist inhaler devices."
Frank also believes sustainability is coming to the forefront in the industry: “One of the best innovations currently in OINDP is a response to sustainability. Regarding pressurised metered dose inhalers, there has been a push to reformulate products with
new propellants which have a low global warming index.”
“This goes back to the Montreal Protocol from the 1980s, when the original CFC propellants were substituted for the HFAs due to the CFC’s unfortunate ability to deplete the Earth’s ozone layer. They were replaced with a whole range of HFA propellants,
usually HFA 134a or HFA 227 because they don't exhibit activity against atmospheric ozone.”
OINDP methods are less invasive, and may allow the avoidance of injectables
“Although they don't interfere with the ozone layer, they have a very high global warming index, so we ended up moving on from one problem to another. Companies are now looking to reformulate into something a more sustainable. To address this problem, the pharmaceutical industry is working to introduce new propellants such as HFA 152. This has a low global warming index, but does still have show flammability issues.”
Not only has sustainability been an area of development in the industry, but so has the development of complex molecules to be used as vaccines: “Biologics is the other area in which we see significant progression within OINDP. There’s a lot of activity currently in the field of nasal sprays, which has been pushed by the COVID-19 pandemic.
“In this category, there has been a movement into assessing more complex molecules, such as mRNA-type vaccines to determine their efficacy in this form. These methods are less invasive, and may allow the avoidance of injectables, which is a big plus for those receiving these treatment types.”
A continuously growing industry
Amid the ongoing expansion of inhaled products, numerous opportunities emerge for the industry to address patients' unmet needs through simpler and potentially more effective administration methods.
Frank concludes, “In my opinion, the landscape regarding groundbreaking pharmaceutical research has shifted over the last 15 years. Innovation now primarily occurs in smaller tech companies and University spin-outs, while large pharma companies have reduced research in small molecule space, focusing more on complex biologics. This presents opportunities for companies like ours as many small enterprises seek assistance in developing and evaluating the viability of their ideas."
