Applications of VCM
Versatile As a Swiss-Army Knife
Implement VCM for all applications benefiting from a geometrically defined thermoplastic sample. Increase the precision of standard measurements and get access to new insights in the fields of:
ASD Formulation Screening
VCM as the Game Changer.
Amorphous solid dispersions (ASDs) are an essential drug delivery technology for the formulation of poorly soluble active pharmaceutical ingredients (APIs). Embedding single API molecules well distributed in a polymer carrier maximizes solubility enhancement. During ASD formulation screening, the aim is to find the best combination of polymers, surfactants, and drug load.
Ø 25 mm
Weight: 5 g
Processing T: 170°C
Ø 20 mm
Weight: 3 g
Processing T: 170°C
Ø 20 mm
Weight: 1 g
Processing T: 170°C
Due to numerous varieties and tests, the number of samples easily ranges into the hundreds considering various polymers and different API concentrations. Since APIs (or NCE; New Chemical Entities) are limited in the early stages, prototyping of new formulations should consume as little as possible. With conventional approaches, the ASD screening method of choice is always a trade-off between the amount of used material, the usability for ASD characterization, and scale-up ability.
Vacuum Compression Molding (VCM)
VCM allows you, for the first time, to lossless prepare extrusion-like samples with a defined shape. Define the material consumption by choosing the sample's geometry (diameter and height) and achieve reliable and repeatable ASD characterization. The smaller the geometry, the less material is required.
A set of three specimens can range from 200µg up to 5g and is prepared in less than an hour. In contrast, the smallest twin-screw extruders require 5g of material per batch, but not in a lossless manner. A good fraction of it is lost in the processing equipment and needs to be tediously cleaned afterwards.
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The emergence of new biomaterials will offer long-acting implants the possibility of significant impact in therapeutic applications. Reducing batch sizes as well as significantly faster prototyping will help to speed-up implant-based development.
⌀ 2 mm
up to 15 mm length
1 - 50 mg required
With rod diameters of down to 0.3 mm, VCM enables lossless implant prototyping in the µg-range. Low yields belong to the past when you develop subcutaneous, intraocular, or intratumoral implants with VCM. Available dimensions are 0.3, 0.5, 0.8, 1 and 2 mm in diameter.
Complex Structures - Multilayer Samples
VCM allows you to fuse multiple layers to one specimen. One can prepare various VCM discs in advance, one by one, and load them into the VCM chamber in the desired order obtaining one single multilayer specimen with distinct layers and a sharp interface.
VCM discs 5 - 25 mm
Multilayer sample with distinct layers and sharp interfaces
VCM is the best preparation method for complex geometries (multilayer or core-sheath structure). Screen formulations with drug-loaded core and diffusion barrier (e.g., contraceptive implants, Intra-vaginal rings) within hours and use them for further investigations like dissolution testing, SEM, OCT, FTIR, and various more.
Our customers have written several publications in the field. Check out the publications page for more information about the IVR Screening of Implants.
Perfect sample, comparable dissolution.
Determining the solubility and dissolution rate are key measures for developing new formulations. Most drugs have a defined therapeutic window, and the final dosage form should meet this therapeutic window to create the desired effect in the human body. For poorly soluble drugs, ASDs are used to increase solubility. The choice of carrier materials and drug loading have a significant impact on the dissolution performance.
Conventionally compressed powder samples consist of many small particles, including many phase boundaries in between. The innovative VCM process fuses all particles to one single body and enables uniformly molten samples without any internal phase boundaries. Only the outer surface is a potential contact area with the dissolution media.
Before VCM, dissolution was not independent of surface area. Different-sized particles were dissolved or detached from a compacted tablet during the trials, resulting in a continually changing surface area and inaccurate dissolution results that were hard to compare between different formulations. With our VCM, intrinsic dissolution approaches will always have a defined surface area that allows uniform dissolution.
Intrinsic Dissolution Testing
Using MeltPrep samples for intrinsic dissolution testing gives valuable insights into formulation characteristics. The defined geometries allow drug-releasing via a defined surface, resulting in more accurate and reproducible results. Thus specific drug release properties can be derived from testing. Use optional cups to enable unilateral testing.
Microscopic Erosion Time Test (METT)
Esther Bochmann of Abbvie in Germany developed this approach. A 50 mg VCM sample is embedded together with the dissolution media between two glass covers. Using a microscope allows taking pictures of the VCM disc periodically and following the erosion. Unlike the dissolution tester, METT forces a 2-dimensional stationary dissolution.
Ø 10 mm
Images of discs erosion after 1 hour
Ritonavir loaded PVP discs with increasing API concentration
Comparing multiple samples with increasing API content shows the maximum load of a specific API polymer combination that leads to erosion. It is the so-called drug dispersibility limit. Find more information in the publication.
Diffusion Studies of Complex Structures
Use VCM multilayer samples to mimic core-sheath structures and investigate long-term drug release. Diffusion Barrier discs as thin as 100µm fused with a drug-loaded core simulates a coextruded cross-section of an intra-vaginal-ring (a marketed product using this principle is the NuvaRing by MSD).
Lateral surface sealed with barrier glue
Looking at the dissolution rate of VCM multilayer prototypes, the comparability to co-extruded versions improves the diffusion studies of complex structures immense. Even with small-scale extruders, obtaining samples requires much time. Co-extruded versions need several extrusion steps for establishing the often desired low concentration, and tedious cleaning afterwards is needed. VCM samples can be taken in one morning and analyzed on the same day. VCM is saving not only material but also precious working time.
Understand Your Formulation Performance.
Knowing the solid-state behavior is essential for developing new ASD formulations. Highlighting the importance of reliable analysis, VCM is a must for solid-state characterization labs.
Samples are placed in a crucible and subjected to a controlled heat transfer cycle. For powder samples, particle boundaries impede heat transfer and lead to a noisy signal. Homogeneous VCM samples ensure uniform heat transfer and more expressive results.
Measurements on two samples with different thicknesses allow to derivate thermal conductivity and heat capacity using a mathematical model from modulated DSC. Both values can be derived from sample quantities lower than 100 mg of material.
MeltPrep has developed dedicated easy-to-use benchtop solutions for combining the VCM Tools with standard process sensors (UNF Port) to analyze molten samples offline. Monitor transitions from powdery state to molten state to solid-state and use the results to choose the most suitable spectroscopy method (NIR, UV-Vis, Raman). Study penetration depth, reflectance, or transmission mode to find the most sensitive configuration and ensure representative results.
Improve Your Material Knowledge.
Most textbooks on different measurement techniques describe uniformity with defined geometries as the key to determining accurate material properties.
Shear Flow Rheology
When studying flow behaviour, an applied shear force deforms the polymer melt within defined measuring geometries, and characteristic material properties are derived. The presence of bubbles distorts the flow field and falsifies the measurement data.
For conventional sample preparation (grey area) a standard deviation of up to 50% was considered reasonable before VCM. VCM's unmatched sample quality enables a reliable and repeatable measurement (blue line) with a standard deviation of less than 3%.
The improved accuracy gives access to study valuable information for the scale-up from VCM to extrusion. Understanding the plasticizing effects of ingredients on polymer-carriers is key. Derive the extruder's processing temperatures from the rheological study with only 1 gram of material and stop wasting materials for trial and error process development.
Extensional Flow Rheology
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 behaviours.
Measurements at low strain rates perfectly fit the conventional derivation from shear rheology. But increasing strain rates lead to strain hardening due to the entangled polymer chains. Shear and extensional flow occur in an extruder and influence the formulation's processability. Understand strang formation at the extruder die and downstream ability.
Dynamic Mechanical Thermal Analysis (DMTA)
DMTA is the basis of understanding polymers' mechanical properties like the glass transition temperature. A reliable and accurate Storage and loss moduli measurements are essential for designing abuse-resistant dosage forms and implants (e.g., subcutaneous or intra-vaginal) with the highest wearing comfort.
To meet the DMTA sample requirements, MeltPrep developed the rectangular VCM Tool. It allows you to prepare flawless samples with a defined and reproducible rectangular shape. Different dimensions are available.
VCM Bar Tool