BEST PRACTICE  

Fast help in small doses

High levels of air pol­lu­tion put a strain on people’s health in urban agglom­er­a­tions and indus­trial cen­ters in China like nowhere else on earth. As a con­se­quence, the number of res­pi­ra­tory dis­eases is rising steadily. For the admin­is­tra­tion of soothing active ingre­di­ents, the Chi­nese com­pany Kin­no­vata is focusing on powder inhalers. The fast supply of inhalers is ensured by a fully auto­matic filling line devel­oped by Harro Höfliger.

China is the largest market of the so-called “pharmerging” coun­tries and the growth of the phar­ma­ceu­tical sector is even above-average in the area of res­pi­ra­tory therapy. The reason for this is the high level of fine dust pol­lu­tion in the met­ro­pol­itan areas, and the resulting res­pi­ra­tory dis­eases affecting their res­i­dents. The demand for med­ica­tion is high and this trend is set to con­tinue. Tianjin Kin­no­vata Phar­ma­ceu­tical Com­pany Ltd., founded in 2013, spe­cial­ized early in the pro­duc­tion and
filling of inhalers (Dry Powder Inhalers, DPI). The active ingre­di­ents con­tained therein in powder form are used for the treat­ment of res­pi­ra­tory dis­eases such as asthma or COPD (chronic obstruc­tive pul­monary disease).

Foto:

When devel­oping the nec­es­sary assembly and filling machines, Kin­no­vata delib­er­ately banked on Harro Höfliger’s know-how and expe­ri­ence. The fully auto­matic machine deliv­ered in May 2016 pro­duces two inhalers per cycle and up to 40 inhalers per minute. The assembly and filling process is com­plex. The bottom parts of the inhaler are stored on a tray in a tray­loader and fed to the assembly line just in time. All other indi­vidual parts are fed into the machine by gripper units and are grad­u­ally assem­bled to form com­plete devices. The machine has been designed in such a way that the indi­vidual parts are fed from the rear side. This makes it easier for oper­a­tors and min­i­mizes their movements.

In order to facil­i­tate cleaning and to pre­vent the large-scale con­t­a­m­i­na­tion of the entire process with active ingre­dient par­ti­cles, the machine designers focused on and inte­grated the so-called walking beam trans­port plat­form: The gripper units used for assembly and trans­port of inhaler parts do not advance through the machine but remain at their respec­tive assembly station.

(Photo: Harro Höfliger)

The powder is filled into both smaller round, and larger rec­tan­gular reser­voirs. This is done without the need for time-con­suming refit­ting – one of the major tech­nical chal­lenges that had to be over­come when designing the machine. Both fill quan­ti­ties are con­trolled inline using weighing tech­nology before the respec­tive reser­voir is closed with a lid. In addi­tion, an inte­grated color sensor ver­i­fies the dif­ferent colors of the two inhaler ver­sions. In the next step the laser coding is applied. For this pur­pose, the inhalers are removed from the trans­port grip­pers, rotated over the laser and marked from below. A camera checks the quality and com­plete­ness of the marking.

Step 1: Sup­plying the device, Step 2: Dosing of powder, Tara weighing and Gross weighing, Step 3: Closing of reser­voir, Step 4: Mounting of trigger and Laser coding

The staff and the man­agers at Kin­no­vata are very sat­is­fied with the machine. Not only have they been con­vinced by the com­plex tech­nology and imple­men­ta­tion of the required process steps, but also by the seam­less col­lab­o­ra­tion with Harro Höfliger. The best proof: Dis­cus­sions are in progress about the man­u­fac­ture of another filling and assembly line for a new gen­er­a­tion of inhalers.

Dosing in the form of powder

Among the so-called “new admin­is­tra­tion forms”, inhala­tion powder is regarded as the method of choice for the intake and absorp­tion through the lungs (pul­monary) or through the nasal mucosa (nasal). The pro­cessing of micronized powder in a fully auto­matic system poses a very demanding chal­lenge in phar­ma­ceu­tical pro­duc­tion, since the pro­cessing method depends heavily on the powder’s phys­ical prop­er­ties. Par­ticle size and geom­etry, size dis­tri­b­u­tion as well as the sur­face struc­ture of the par­ti­cles affect the powder’s flow behavior.

The effect of par­ticle size

1) Mouth and throat region, 2) Tra­chea Bronchial tubes, 3) Alveoli

Powder inhalers have proven to be effec­tive for the admin­is­tra­tion of active ingre­di­ents – for example in the treat­ment of asthma. The graphic shows how inhala­tion par­ti­cles are deposited in the res­pi­ra­tory system depending on the diam­eter. With its micro-dosing sys­tems, Harro Höfliger covers a wide spec­trum of con­ceiv­able par­ticle size dis­tri­b­u­tions, starting at diam­e­ters below 1 μm.

Mrs. Li, why did you choose Harro Höfliger to develop your process?

Jing li, Man­aging director at Tianjin Kin­no­vata Phar­ma­ceu­tical Com­pany ltd.

”Harro Höfliger con­vinced us with their tech­nical exper­tise. The
machine con­cept they pre­sented is excel­lent and fully imple­ments our require­ments. In addi­tion, we were impressed by the numerous inhaler machines that Harro Höfliger has already imple­mented. This gave us the nec­es­sary assur­ance during our deci­sion-making process.

But tech­nology was not the only deci­sive factor. The good coop­er­a­tion with Harro Höfliger and their rep­re­sen­ta­tive Rieck­er­mann was also cru­cial for our deci­sion. And as we can now see from the flaw­less oper­a­tion of the machine, we made the right decision.”

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Photos: Janine Kyofsky, Helmar Lünig, Raff Digital