Worldwide, 400 million individuals suffer from allergicrhinitis, the most prevalent type of allergy that includes hayfever and allergies to things such as mould, plants, dust andanimal dander.1 The topical nasal allergy market is currentlyestimated to be worth some US$2.5bn annually, and thenumber of sufferers shows no signs of diminishing, leading tothe continuing search for medication to alleviate symptoms.2

The current treatment of choice for many sufferers,particularly those who wish to avoid systemic medication, is theaqueous pump spray containing corticosteroid activepharmaceutical ingredients (APIs) such as fluticasonepropionate, mometasone furoate monohydrate, andbeclometasone dipropionate. These ‘wet’ sprays have becomewidely used since chlorofluorocarbon (CFC) propellants werephased out of use in the 1990s, halting the marketing of thepreviously popular ‘dry’ nasal Metered Dose Inhalers (MDIs).

Patient dissatisfactionHowever, there is a degree of dissatisfaction with the currentlyavailable therapies – users report them to be inconvenient andeven embarrassing to use in public due to the immediate liquidrun-off, and unpleasant due to the post-nasal drip down thethroat, which can result in an uncomfortable sensation andaftertaste.

Allergies have a considerable effect on quality of life –particularly if they are of the perennial variety (PerennialAllergic Rhinitis, or PAR) as well as seasonal (Seasonal AllergicRhinitis, or SAR). As patients have become better informed andmore vocal about treatment preferences, demand for analternative solution to inconvenient aqueous sprays is growing.

There is also growing interest in nasal drug delivery to treatconditions beyond the nasal allergy market. The nasal cavityhas proven to be an effective route of administration forsystemic delivery due to the high permeability of the nasalmucosa, the plentiful vascularisation, and the ease ofadministration versus delivery methods such as injectables.Nasal delivery technologies are progressing, and attempts tomitigate the drawbacks of traditional nasal therapies, such asrunning liquids and the use of locally irritating absorptionenhancers, are being offered by several companies.3

Support for MDIsMDIs have been available since 3M introduced the first aerosolto control asthma in 1956, and have made significantadvancements due to increased regulatory requirements andtechnology development to increase efficacy and patientcompliance. MDIs rely on a propellant, and it is well-known thathydrofluoroalkane (HFA) has replaced chlorofluorocarbon(CFC) as the driving force of the formulation. The valves inMDIs have also seen improvements to accommodate the newHFA propellants. With these two significant developments,MDIs now meet more stringent regulatory requirements ondosing uniformity and extractables and leachables.4

Building on the success of MDIs in the asthma and chronicobstructive pulmonary disease (COPD) markets, nasal MDIswere widely used for nasal allergic rhinitis, but were notincluded alongside pulmonary MDIs in the ‘essential use’exemption in the Montreal Protocol.5 Manufacturers turned toaqueous pump sprays as a shortcut to keeping their products inthe market. However, patient dissatisfaction quickly surfaced,with calls for the return of key aerosol brands. This resulted inthe reformulation of nasal MDIs with HFA propellants.6

Two products were approved by the FDA during 2012,bringing nasal MDIs to the market once more, nowincorporating HFA propellants for the very first time. Zetonna(ciclesonide) MDI from Sunovion promises a once-a-day HFAaerosol technology which delivers fine aerosolised particles

directly to the nasal passages.7 Qnasl (beclomethasonedipropionate) MDI from Teva promises a waterless mist thatensures that 99% of the medicine stays in the nose, at 45seconds after spraying.8 Both of these products incorporate thelatest aerosol technology and drug delivery devices includingdose counters. With these developments, and others in theasthma and COPD category, it seems that the MDI is as popularwith patients and manufacturers as ever.

Patient preference studiesNasal MDIs allow medication to be administered via a quickly-evaporating, no-drip spray and can give patients freedom fromtheir seasonal or perennial allergies in a convenient and fast-acting format.

In a user study conducted by 3M, 50 subjects (all current

September 2014 manufacturing chemist xi

Nasal MDIs have the potential to reach far beyondthe current usage sphere of allergic rhinitis.Louise Righton, Global Marketing OperationsManager, 3M Drug Delivery Systems, looks at whythey may see wider therapy use in future

Nasal MDIs –movingbeyond nasalallergy

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The Nasal MDIproducced by 3M

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users of aqueous sprays for allergic rhinitis) were provided witha prototype of 3M’s Nasal MDI and asked to rate it comparedwith their current aqueous pump spray device. This studyshowed how highly nasal comfort was valued – prior to tryingthe 3M Nasal MDI, users were asked what they look for in adevice, and the results are shown in Figure 1.

Subjects’ initial impressions of the 3M Nasal MDI were highlyfavourable due to its ‘twist-and-lock’ design, and once the devicehad been trialled by spraying a placebo ethanol-containingformulation once in each nostril, preference was clear. The userstudy showed more than three-quarters of subjects preferredthe 3M Nasal MDI to their current aqueous pump spray device(Figure 2).9

The primary factors that influenced this decision were: nodripping down the nose or post-nasal drip in the throat; theinclusion of a dose counter; and the metered dose, which gaveconfidence that the right level of drug had been delivered to thenasal cavity. Ease of use, no aftertaste and a comfortable sprayforce were also complimented.9

Interestingly, this study confirmed that many of the concernsand discomforts associated with an aqueous nasal pump sprayare diminished when nasal MDIs areintroduced.10 Nasal MDIs shouldtherefore be considered as a ‘new’ form ofdrug delivery that represents a stepforward for patients.

The findings in the 3M study point tothe need to include patient preferencesand compliance aspects in devicedevelopment – perhaps an obvious point,but one that many developers overlook infavour of technological advancements.

For example, the metered dose which isinherent in an MDI, but missing from anaqueous pump spray, is highly valued bypatients, adding to their confidence that the dose has beentaken correctly. This inherent feature ensures the inhalerdelivers one pre-determined metered dose per spray, regardlessof how hard the actuation button is pressed.

This important feature differentiates from the force-dependent aqueous pump sprays, from which delivered dose canvary significantly, and patients realise this. In the preferencestudy conducted by 3M, the metered dose was the third most

valued feature of the 3M Nasal MDI, after the no-drip spray andthe dose counter.

A dose counter gives patients confidence that a complete dosehas been dispensed based on the visual indication provided bythe counter on the 3M Nasal MDI. They no longer have towonder about how much medication is left in the device or whenit should be replaced.

3M has developed a nasal MDI that meets all of these desiredcharacteristics, and also includes a twist-and-lock design whichintegrates the cover with the actuator, for ease of use on-the-go.

Nasal – the next drug delivery format?Patients have more influence than ever before over how to treattheir conditions. Major opportunities exist for those who canimprove the user experience with an innovative drug deliverydevice.

In today’s digital world, patients have ready access to productinformation, reviews and forums, and those who are dissatisfiedwith the products they depend on often research alternatives. Inthis environment, pharmaceutical companies need to be moremindful of developing treatments that keep user-friendlinessand compliance at the forefront.

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‘’Many of theconcerns anddiscomfortsassociated withan aqueousnasal pumpspray arediminished whennasal MDIs areintroduced”

‘’Companiesneed to be moremindful thanever before ofdevelopingtreatments thatkeep user-friendliness andcomplianceat the forefront”

Figure 2: 76% of study participants preferred the 3M Nasal MDI to their current pump spray device9

Figure 1: Importance of characteristics when choosing a nasal spray9

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3. www.drug-dev.com/Main/Back-Issues/PAIN-MANAGEMENT-Rapid-Action-Therapy-in-Pain-Relie-611.aspx. Accessed on 1 December 2013. 4. http://solutions.3m.com/3MContentRetrievalAPI/BlobServlet?lmd=1316754965000&locale=en_WW&assetType=MMM_Image&assetId=1273695586782&blobAttribute=ImageFile. Accessed on 15 July 2014.5. http://ozone.unep.org/new_site/en/essential_use_information.php.Accessed 5 August 2014.6. www.medkb.com/Uwe/Forum.aspx/sinusitis/1440/Return-of-the-Aerosol-Steroid-Nasal-Spray. Accessed on 5 August 2014.7. https://www.sunovionprofile.com/sp/zetonna.html. Accessed on 5 August2014.8. http://qnasl.com/. Accessed on 5 August 2014.9. Proprietary 3M patient research conducted in USA, September 2012.10. http://www.ondrugdelivery.com/publications/Pulmonary%20Nasal%20May%202013/Pulmonary_Nasal_May_2013_Low_Res.pdf 11. Migraine Therapeutics Market in the US: Market Forecast, Patient Flow,Competitive Landscape, and Pipeline Analysis. Commercial Insights, July2011.12. PharmaCircle. www.pharmacircle.com/. Accessed 30 July 2013.

N.B. Zetonna is a registered trademark of Takeda GmbH and Qnasl is aregistered trademark of Teva Respiratory, LLC.

CONTACT3M Drug Delivery Systems 3M Center, Building 275-03-E-10 St Paul MN 55144-1000, USAT +1 888 364 3577http://solutions.3m.com

Nasal MDIs have the potential to reach far beyond thecurrent usage sphere of allergic rhinitis. Three nasal migraineproducts are already on the market in the US and elsewhere,based on two APIs – sumatriptan succinate and dihydro-ergotamine mesylate – with 11 more nasal products in thepipeline for migraines.11

Similarly, eight nasal products are marketed for osteoporosis,based on two APIs – calcitonin (salmon) and elcatonin, withnine in the pipeline.12 Urinary incontinence, diabetes,neurodegenerative conditions, anxiety and depression, and painare all categories with nasal drug delivery potential and currentR&D activity.

Consideration of the user experience in these conditions iskey. By creating products that patients find practical and easy touse, companies can better ensure their products are wellreceived.

Nasal MDIs have been demonstrated to be user-friendly,convenient and the preferred method of drug delivery forallergic rhinitis in the user-trial setting. By catering to patientpreferences, companies can stay at the forefront and improvethe quality of many patients’ lives.

REFERENCES1. Global surveillance, prevention and control of chronic respiratory diseases: acomprehensive approach, World Health Organization, Geneva, 2007. AndAsthma Foundation. www.asthmafoundation.org.au/rhinitis.aspx. Accessed 3 May, 2013.2. The Asthma, COPD & Allergic Rhinitis Market Outlook to 2016. BusinessInsights, May 2011.