Is the capsule filling process altering dry powder inhaler performance?
The filling process of capsules is of great importance. Powders do have a memory of how they have been processed, so the capsule filling process could have a strong effect on how in the end the active drug is delivered to the lungs of the patient. So that is what we want to test.
What happens during inhalation?
During an inhalation a patient will take the device and start inhaling. At that moment the powders are fluidized. During fluidization the small particles of the drug are released from the surface of the coarse lactose and it is well known that fine grades of lactose do facilitate this process. So if there are more fines present also more of the drug particles will be released from the coarse surface.
Why is this study important for the formulator?
The formulator normally will make the first formulation on lab scale. They quite often use hand-filling systems, and from the lab-scale development they will go to a production scale in a later phase of their formulation development.
Knowing that you can choose the right type of lactose that can help you in speeding up your development from start until production scale.
Does the type of fine lactose have an impact?
The type of processing has an impact on the release. It is known that the fine lactose and especially the really fine types of lactose do have a very strong effect on the release mechanisms.
What was the approach taken?
We have looked at different lactose fines in combination with a coarse grade of lactose and looked at different filling techniques: hand filling as well as vacuum filling with low vacuum and high vacuum and looked whether this had an effect on the reproducibility of the dosing as well as at the fine particle fraction in the formulation.
We filled our capsules with lactose and an active, budesonide. We blended them together. As lactose we took a coarse lactose and we also put in fine grades of lactose. So we got in total four different mixtures of lactose with budesonide with a coarse grade, one with a milled fine grade another type of milled fine grade and at the end a coarse grade with a micronized fine grade. So a Lactohale 100 with a Lactohale 210, Lactohale 230 or Lactohale 300.
How did you measure performance?
Well we took the capsules. We put them into a cyclohaler and did in-vitro testing with a NGI to measure the fine particle fraction.
Does the filling process alter the performance?
If you look at this study you see there is no significant effect when we add in different fine lactose grades if you have micronized fines or if you have slightly milled or strongly milled fines we didn’t see any effect on the fine particle fraction and on the filling process. We could use hand filling or vacuum filling and we still have the same performance. So this is very important for the formulator to know. If we didn’t add any fines into the formulation we saw there was a slight difference between the dosing of the drug out of the device, but that part we cannot really explain at this moment.
What is the benefit for the formulator?
Well what we have shown here is that if you take the right type of lactose it is easy to scale up from hand-filling to machine filling, because we did not see any difference. Especially in the grades where there are fines present in the lactose. So it is important to choose the right type of lactose, and then it is easy to scale up for a formulator.
With the results of this study you can really see that different fines will have different effect on the fine particle fraction. And DFE Pharma is able to offer these different grades to help the formulator.
Have the conclusions provided new insights for the formulator?
Actually we were quite surprised by the outcome, because initially we thought that taking a different way of filling a capsule will have a big effect on the powder as powders do have a memory effect. In fact we did not see this large effect; actually in most cases we did not see any effect. So we were quite surprised by that.
What if people still have questions?
If people still have questions if they have seen this video where we have tried to explain a little bit more about our study they always can contact DFE Pharma for additional information.