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Devel­oping a new inhaler is a labo­rious process. Exten­sive tests are required to ensure that the device truly works. The more com­plex it is, the greater the number of design and man­u­fac­turing rela­tion­ships that have to be deter­mined, and the more mal­func­tions can occur: during an inhaled com­bi­na­tion devel­op­ment, phar­ma­ceu­tical com­pa­nies have to con­sider not just the drug product and device, but also how they interact with each other. This is often reflected in the devel­op­ment time and costs.

Hov­ione Tech­nology wants to help these phar­ma­ceu­tical com­pa­nies enter the market faster and has devel­oped the ­Papillon dry powder inhaler for this pur­pose. The name – Papillon is the French word for but­terfly – says it all: The device aims to be simple and light. Because unlike other inhalers, which can con­sist of up to 26 com­po­nents, it only con­sists of two reusable plastic com­po­nents and one blister.

“The Papillon is designed so simply that phar­ma­ceu­tical com­pa­nies only have to test a few func­tions before starting devel­op­ment.”João Ven­tura Fer­nandes, Director of Tech­nology Devel­op­ment and Licensing at Hov­ione Technology

Insert the blister, close the device, inhale: Thanks to its simple design, it is easy for patients to use.

This makes it easy to pro­duce and reduces the com­plexity and cost. João Ven­tura Fer­nandes, Director of Tech­nology Devel­op­ment and Licensing from Hov­ione Tech­nology explains: “A lot can go wrong with com­plex devices and data shows that inhaled drugs can be deliv­ered as effec­tively from devices made of very few parts and assembly steps. The Papillon is designed so simply that phar­ma­ceu­tical com­pa­nies only have to test a few func­tions before starting devel­op­ment. This saves time and money, so that focus can be put on powder development.”

Easy patient use

The Papillon was also designed for easy patient use: They only need to insert the blister and close the device and then they can inhale. For the next inhala­tion, they simply insert a new blister, because the Papillon can be reused many times. This way, it hardly gen­er­ates any waste. “We want to make life easy for patients while at the same time improve the en­vironmental sus­tain­ability of inhalers,” says João Ven­tura Fernandes.

Phar­ma­ceu­tical com­pa­nies can use the dry powder inhaler in many dif­ferent appli­ca­tion areas. This is because the design can be adapted to an indi­vidual or double blister con­fig­u­ra­tion. The double blister ver­sion makes it pos­sible to admin­ister two sep­a­rate pow­ders in par­allel and simul­ta­ne­ously. The inhaler is also suit­able for acute treat­ments, such as an antibi­otic admin­is­tered in a high dose to combat a lung infection.

The pro­duc­tion and filling of the sample blis­ters for the Papillon takes place directly at Harro Höfliger. After deep drawing …

… the sample blis­ters are filled …

… and then singularized.

Many dif­ferent powder technologies

Dif­ferent phar­ma­ceu­tical com­pa­nies are cur­rently testing the device with their for­mu­la­tions. The right filling tech­nology plays a key role here. João Ven­tura Fer­nandes says: “Harro Höfliger has a great deal of know-how and a wealth of expe­ri­ence in powder filling. No other machine man­u­fac­turer offers as many dif­ferent tech­nolo­gies for filling powder. By coop­er­ating with Harro Höfliger, we make it even easier for our cus­tomers to use our inhaler for their pur­poses and, fol­lowing devel­op­ment, to smoothly scale-up to indus­trial-scale filling for com­mer­cial stages.”

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If a cus­tomer shows interest in the Papillon, Harro Höfliger car­ries out pre­lim­i­nary filling tests with their powder as the first step. Then Harro Höfliger sends filled sample blis­ters to Hov­ione Tech­nology or the end cus­tomer so that they can test whether the inter­ac­tion of the device and powder works. It is extremely com­plex, because all pow­ders behave dif­fer­ently. Some flow well, others lump. In addi­tion, the dif­ferent filling tech­nolo­gies affect the powder to dif­ferent degrees, for example due to the shear or com­pres­sion forces. Finally, the adhe­sion forces between powder par­ti­cles must be over­come in the inhaler. Only then can the powder be so finely dis­persed that the active ingre­dient pen­e­trates deep enough in the patient’s lungs and does not get stuck in the throat or in the upper airways.

Nothing is impossible

But what hap­pens if the inter­play does not work at first? Marco Laack­mann, Director Inhala­tion Tech­nology at Harro Höfliger, says: “Harro Höfliger is dis­tin­guished by the fact that we can also over­come spe­cial chal­lenges – for example, filling unusual pow­ders.” In their Pharma Ser­vices depart­ment, Harro ­Höfliger offers exten­sive options for opti­mizing the filling process for the respec­tive powder.

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Laack­mann explains: “In one past project, for example, the metered powder slug was too large, so the inhaler did not work fully. Instead, we filled it with sev­eral small powder slugs. That worked.”

During product devel­op­ment, the filling process is always the first thing to be sorted out. If no solu­tion can be found, adjust­ments can also be made to the blister or device to opti­mize them. If this also does not result in any improve­ment, the for­mu­la­tion can be adjusted. Laack­mann sums it up: “Per­haps it is not always as easy as the flap of a butterfly’s wings. But together with Hov­ione Tech­nology, we will always find a solu­tion so that cus­tomers can use the Papillon for their formulation.”

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Photos: Hov­ione Tech­nology, Illus­tra­tions: Megan Bird