Which active ingredients are suitable for applying HME technology?
BCS class II-IV active ingredients with absorption (bioavailability) and permeability difficulty. Highly thermosensitive active ingredients can usually not be processed.
At what scale can HME formulations be produced at Losan?
For screening, we can produce very small batches using established tools (e.g., Meltprep). In this case, we can get by, for example, with 50 mg. At laboratory scale on our Pharma 11, we can produce sizes from 20 g up to several kg. The pilot and production scale on our Leistritz 27 Micro is suitable for throughputs from 1 kg/h up to 25 kg/h.
How are the extrudates cooled after the melting process?
At Losan, various cooling techniques are available depending on the subsequent application. If pellets are required, then extruded strands are cooled with a cooling belt. If a high throughput and fast cooling of the melt is required, we use a cooling drum.
How are the HME granules comminuted after the extrusion process?
The extrudates can be comminuted to the desired particle size via a granulator (cylindrical particles), via an oscillating mill, a conical mill or a hammer mill. From granules to fine powder, everything is possible.
What’s the typical throughput for melt extrusions on Losan’s equipment?
The type of formulation, loading of the extrudate and its cooling properties significantly influence the throughput. However, generally throughputs of at least 8 kg/h can be achieved.
What factors influence the stability of HME granules?
The most important influencing factors are the selection of polymers for stabilizing the amorphous active ingredient and the loading of the active ingredient. In terms of chemical stability, the right choice of stabilizing excipients plays a role (antioxidants, pH modifiers).
What is the risk of observing recrystallization of the amorphous active ingredient in the products’ storage process?
After careful formulation development with the Losan Screening Tools, there is little risk and no recrystallization is observed in the stabilities used to define the product shelf life. However, there is a risk if the active ingredient is only amorphously encapsulated rather than molecularly dispersed, and this aspect must be carefully checked in the accompanying stability studies.
Can high-melting active ingredients with a melting point > 200°C also be encapsulated?
Encapsulation is possible, but very often these active ingredients are then not dissolved in the polymer and continue to be present in crystalline form. During the process, the active ingredient can be subjected to very high shear stress, depending on the selected configuration of the extrusion screws. This can allow the active ingredient to be comminuted down to nanoparticles or amorphous encapsulations. Such a formulation could also lead to increased absorption in the body.
Can the active ingredients recrystallize in vivo when the HME matrix is dissolved and then precipitate? What happens then and how is this taken into account in formulation development?
Any drug precipitation during GI passage can affect the bioavailability of the drug – in other words – formulation development aims to achieve the most robust dissolution. Most interestingly, significantly improving absorption in vivo through solubilizing formulations remains difficult, as indicated by the very limited number of successful market products. It is well known that bioavailability in vivo rarely reaches a comparable magnitude to dissolution enhancement in vitro. This is where the new Losan screening technology comes in, linking drug release from the formulation and permeability. The nanometre-scale supramolecular structures that may form during release, such as micelles, nanoparticles, oil droplets or excipient-drug complexes, can therefore be included in formulation development.