What can it be used for?
Preparing flawless samples.
​
Most textbooks on different measurement techniques describe the uniformity with defined geometries as the key to determining accurate material properties. The VCM technology was originally developed for preparing samples for rheological measurements.
Rheology (Discs 8-25 mm & Bars 10x40 mm)
When studying flow behavior, samples are deformed within defined measuring geometries and characteristic material properties are derived. When bubbles are present, the flow field is distorted and the measurement falsified.

Homogenous

vs.
Bubbles

Homogenous
vs.

Bubbles
Early rupture
Extensional rheology requires homogeneous bars to obtain results. No sample preparation starting from powders existed so far. VCM opens the opportunity for the first time. New insights help to understand material and processing behaviors.

What else?
Surpassing your expectations.
Our customers use the flawless VCM samples for various measurement methods such as DSC, hardness, notch impact strength, heat capacity, solubility, DMTA, microscopy etc. Below is a short excerpt of one of the most frequently requested measurement methods.
DSC Measurements (Discs 5 mm)
Samples are placed in a crucible and subjected to a controlled heat transfer cycle. Particle boundaries hinder heat transfer. Homogeneous VCM samples ensure uniform heat transfer and will lead to more significant results.
Heating Unit
Powder
VCM sample

1st
heating
1st
heating
DSC
crucible
Phase
Boundaries
Homogeneous
Vacuum Unit

Moreover, thermal conductivity and heat capacity can be derived via a mathematical model from modulated DSC measurements on two samples with different thicknesses. Both values can be derived from sample quantities lower than 100 mg of material.

0.4 mm
3 mm


What about prototyping?
Nothing easier than that.
Pilot plants and six-digit Euro investments were required for prototyping of pharmaceutical dosage forms with melt-processed carriers in the past. Now, the VCM technology enables rapid prototyping at a fraction of costs and time required for traditional prototyping methods.
Dissolution (Discs 5-25 mm)
MeltPrep samples can be used for intrinsic dissolution testing giving valuable insights into formulations characteristics. The samples have defined geometries and release the drug via a defined surface, thus specific drug release properties can be derived from testing. Optional cups can be used to enable unilateral testing.
Heating Unit

Noyes-Whitney equation

Intrinsic dissolution rate
Vacuum Unit

Cup
Sample
Dissolution
vessel

Spectroscopy (Discs 25 mm)
MeltPrep has developed dedicated easy-to-use offline solutions for combining the VCM Tools with common process sensors to analyze molten samples offline. The results can be used for designing the probe position for inline implementation.



What about mixing?
Empower diffusion.
To empower diffusive mixing, it’s important to obtain a starting material which is homogeneous in the small micrometer range.
Pellets
If you work with heterogeneous materials at large particle sizes and process it via VCM, you will obtain a heterogeneous sample. VCM is not applying no mechanical mixing inside the Chamber. To illustrate this, we have chosen to fuse multi-colored pellets in the mm-size range with VCM. They are squeezed and melted together, forming a solid disc without air inclusions but the individual pellets with a sharp interface are still visible.
Heating Unit




Pellets
Pellets (length scale = mm range)
VCM Processing
Mixing


One solid disc,
individual pellets visible.
Empowering diffusion is key to obtain a homogeneous sample out of heterogeneous starting materials. We can reduce the particles’ size by starting with a physical powder mixture. After the VCM processing, the result is better than the previous one but there are still some agglomerates and inclusions which are not completely dissolved. This might be due to insufficient mixing or too large particle sizes in general.
Powder
(HPMCAS)
Tracer




+
Mixing
VCM Processing


Inhomogenous sample with API crystals.
Empowering diffusion
To obtain diffusive mixing it’s important to have a starting material which is homogeneous in the small micrometer range. Our customers usually apply a milling step, preferably under cryogenic conditions. After VCM processing the result will be a homogeneous and defined sample that has properties comparable to extruded formulations.



Cryo Milling




Route 1: Milling

+
Powder (HPMCAS)
Tracer

Route 2: Solvent casting


Ethanol

Mixing Powder [5g] and tip of spatula with 100 ml Ethanol.


Let the solution evaporate until a thin layer remains




Homogenous sample.
Amorphous


Homogenous sample.
Amorphous
Another way to empower diffusion is particle dissolution via solvent casting. We can use suitable solvents (ethanol, acetone), let the particles dissolve in it and pour the solution on a Petri Dish. Afterwards we let the solvent evaporate until we obtain a thin thin layer of our materials. The layer is peeled off from the Petri Dish and transferred into the VCM Tool with which a homogeneous sample after is obtained after processing.
Is that all?
Not even close.
The VCM Technology enables the production of multilayer samples. Layers of different materials are prepared one by one. Subsequently, the layers are stacked in the desired order and loaded into the VCM Tool. By performing an additional VCM cycle they are fused to one solid multilayer sample
Diffusion Studies (Discs 8-25 mm)
Multilayer samples are requested in galenics to study drug diffusion and release. They are also used for controlled release drugs. A well-known example is the intra-vaginal birth control ring (IVR) from Merck (NuvaRingâ„¢).
Heating Unit
Drug loaded core

Diffusion barrier

100 μg
4 mm
Diffusion barrier
100 μg

Lateral surface
sealed with
barrier glue
e.g. Ø10 mm
Vacuum Unit

Cross
section
IVR e.g. Ø 50 mm
Drug loaded core
Diffusion barrier
VCM preparation < 1 day
vs.
Conventional co-extrusion > weeks
Eder et al. (2017)
Standard dissolution testing and surface corrections lead to similar results. In many cases there is no need for executing pilot scale experiments.

Similar results
at a fraction of the
cost and time
