Step by step to achieve the per­fect inhala­tion powder

It’s a long journey before an inhal­able API powder comes onto the market. So it is a good thing that Harro Höfliger has experts who know exactly where the journey is going. They use their expe­ri­ence and exper­tise to explore the fastest and safest way to reach the destination.

For some time now, growing num­bers of phar­ma­ceu­tical com­pa­nies are focusing more on dis­trib­uting rather than researching and devel­oping phar­ma­ceu­ti­cals them­selves. They are increas­ingly buying semi-fin­ished or fin­ished for­mu­la­tions from smaller com­pa­nies or star­tups. The rea­sons for this are fairly obvious: The ini­tial devel­op­ment of new drugs is labo­rious, cost-inten­sive and risky. Nobody knows whether there will be an approved and mar­ketable drug at the end of the road. One of the more common stum­bling blocks relates to process devel­op­ment, which may be inad­e­quate or comes too late. Smaller com­pa­nies often lack the nec­es­sary exper­tise and tech­nical options for this task. Harro Höfliger has both: The spe­cial­ists accom­pany and sup­port cus­tomers with a bundle of ser­vices on their way to turning an idea into a product – quckly and with min­imal risk. We’ll show you how such a ­shared journey pro­ceeds by taking the example of an inhal­able powder.


Marco Laack­mann, Sales Director Inhala­tion Tech­nolo­gies at Harro Höfliger

Marco Laack­mann is one of THE inhala­tion experts at Harro Höfliger. As a sales rep­re­sen­ta­tive, he is the first point of con­tact for cus­tomers in many cases. In his dis­cus­sions it is impor­tant for him to under­stand the wishes or ideas and find out ­where the journey should actu­ally go. “Some­times there’s merely a con­cept, but often the cus­tomer already has a sample of the powder they’ve devel­oped. We also have cases where the focus isn’t on the API but on the route of delivery, such as a novel inhaler. And then there are cus­tomers who need our sup­port in devel­oping the powder itself,” Laack­mann explains. Regard­less of the starting sit­u­a­tion: Together with the cus­tomer and experts from Harro Höfliger, he focuses on process devel­op­ment at an early stage, thus set­ting the course for the suc­cess of their project.


Harro Höfliger offers cus­tomers an entire cat­alog of con­sulting ser­vices. These range from ana­lyzing the powder com­po­nents and the sub­se­quent pro­duc­tion of the mix­ture, to searching for an appro­priate filling tech­nology and a suit­able inhaler, up to devel­oping a high-per­for­mance line for com­mer­cial series pro­duc­tion of the fin­ished product.

Regard­less of whether cus­tomers go for indi­vidual con­sulting mod­ules or the com­plete package: The risk of errors in early process devel­op­ment is reduced, which increases the chance of quickly bringing a viable drug to market that can be pro­duced in large amounts.


The first stop in process devel­op­ment is with Dr. Elke Stern­berger-Rützel, Divi­sion Leader Pharma Ser­vices at Harro Höfliger. Together with her team, she ensures that each powder can be processed per­fectly and ends up where it is sup­posed to: firstly in the pri­mary pack­aging mate­rial and later in the patient’s lungs. Prior to starting the actual work, the safety datasheet of the API to be ana­lyzed is reviewed and an iden­tity test ensures that it matches the powder sample sent by the cus­tomer. The phar­ma­cist then under­takes phys­ical char­ac­ter­i­za­tion of the powder.

“Putting it simply, some are like sugar, so they’re flow­able. Others are more like pow­dered sugar, so they’re cohe­sive, i.e. poorly flow­able,” says Stern­berger-Rützel. Based on the analyses, the Pharma Ser­vices team cre­ates met­rics and com­pares them with the ref­er­ence pow­ders avail­able in large num­bers at Harro Höfliger. “At this point,” Stern­berger-Rützel explains, “we can already pre­dict with a fair degree of con­fi­dence whether it is pos­sible in prin­ciple to fill the powder on a large scale.”


One of the trick­iest tasks in process devel­op­ment is mixing the API with excip­i­ents like lac­tose and pos­sibly mag­ne­sium stearate. At the end of the day, the mix­ture must have optimum flowa­bility and an even API distribution.

Dr. Elke Stern­berger-Rützel, Divi­sion Leader Pharma Ser­vices at Harro Höfliger

To achieve this, Elke Stern­berger-Rützel and her staff need a ton of patience: “The main para­me­ters we look at are the con­stituents, as well as mixing speed and dura­tion. We have to adapt both to the par­tic­ular API, because not every API can tol­erate high shear forces during mixing, for example.” Each mixing exper­i­ment is fol­lowed by sam­pling at ten dif­ferent points. “Only when the same active sub­stance con­cen­tra­tion is present at each mea­suring point do we move on to the next step,” says the pharmacist.


The core prin­ciple of dry powder inhalers is that the patient inhales and the air flow makes the powder dis­perse. The ­finer frac­tion ends up deep in the lungs. So what had first been mixed with care and patience must now sep­a­rate again per­fectly. With the aid of numerous tests, the experts deter­mine the ideal inter­ac­tion of inhaler and API particles.

The inter­ac­tion must be just strong enough for the par­ti­cles to adhere to each other during filling, but reli­ably sep­a­rate from each other again during inhala­tion. “We have a Next Gen­er­a­tion Impactor (NGI) for the tests, which works like an arti­fi­cial lung,” Stern­berger-Rützel explains. “With this device, we can accu­rately deter­mine the aero­dy­namic par­ticle size dis­tri­b­u­tion during inhala­tion to ascer­tain whether the powder is sep­a­rating as required.”


For each powder, it is nec­es­sary to select the suit­able filling tech­nology, of which there are around 15 at Harro Höfliger. Stern­berger-Rützel says: “The amount of powder and the API con­cen­tra­tion in every single dose must be per­fectly suit­able throughout, in small batches for clin­ical trials as well as for series production.”

The Pharma Ser­vices team car­ries out filling exper­i­ments with a pre-selec­tion of two or three filling tech­nolo­gies. “We first under­take exper­i­ments man­u­ally with tabletop instru­ments and start with filling the powder into cap­sules. If pre­cise dosing can be demon­strated here, the process will also work depend­ably and repro­ducibly when filling into other devices and in large amounts. This ­gives cus­tomers peace of mind before they enter into major investments.”

every­thing is pos­sible now

Prior to and during the numerous analyses and tests that the powder has to undergo, experts from Harro Höfliger also advise cus­tomers on devices, on request. “We help turn ideas into real prod­ucts,” Marco Laack­mann explains, adding: “Here, too, we have the exper­tise and tech­nical pre­req­ui­sites to carry out sound exper­i­ments.” Elke Stern­berger-Rützel, who doc­u­ments all analysis and exper­i­mental results as well as the process para­me­ters of the powder and makes them avail­able to the cus­tomer, adds: “We take a holistic view of process devel­op­ment. Our approach is to bring for­mu­la­tion, device and filling tech­nology together as early as pos­sible to quickly arrive at the optimal process.”

“The demand for con­sul­ta­tion in process devel­op­ment is already high. And it is set to rise,” Laack­mann is con­vinced. “For instance, with the growth of biotech drugs and APIs like inhal­able anti­bodies or mRNA, entirely new devel­op­ment chal­lenges arise for all involved. We will not abandon our cus­tomers on this path. We accom­pany them on request – from powder devel­op­ment to the con­struc­tion of a com­mer­cial pro­duc­tion line.”

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Photos: Andreas Dalferth