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:
Formulation screening
Dissolution studies
Solid-state characterization
Mechanical characterization
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
Processing T: 170°C
Weight: 5 g
HPMCAS
Aquasolve™
Ø 20 mm
Processing T: 170°C
Weight: 3 g
Klucel™
HPC
Ø 20 mm
Processing T: 170°C
Weight: 1 g
PVP
Kollidon®
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)
Manufacturing ASDs is essential for formulating poorly soluble APIs. VCM allows you, for the first time, to lossless prepare extrusion-like samples with a defined shape without wasting material. 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.
The obtained solid specimen can be used directly for analytics or mill and utilized like any extrudate. Various geometries allow you to process the amount you want to use. Starting from the µg-range, you can go up to a few grams. Unlike the shear mixing in twin-screw extrusion, VCM empowers diffusion for mixing. The smaller the particles are, the more dominant the transfer via diffusion gets compared to shear. Small particles (<100 µm) will give extrusion-like VCM results without the risk of shear degradation.
heterogeneous
One solid disc, but
individual pellets visible
Small particles empower diffusion for mixing
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.
Implants
The emergence of new biomaterials will offer long-acting implants the possibility of significant impact in therapeutic applications. VCM Rod Inserts help to reduce batch sizes and significantly speed-up implant-based development. Due to the lossless process, more formulation ideas get a chance.
⌀ 2 mm
up to 15 mm length
1 - 50 mg required
VCM enables micro implant prototyping. Low yields (<10%) belong to the past when developing subcutaneous, intraocular (fits into 24 gauge needle), or intratumoral implants with VCM. Custom geometries are available on request.
0,5 mm
1,5 mg
0,3 mm
0,2 mg
2 mm
40 mg
20 mm
660 mg
Once the formulation has been identified, the formulation can be scaled towards an extrusion process to enable manufacturing at scale. Material science (e.g., Rheology) performed on VCM samples can help along the way to designing ideal processing equipment.
Complex Structures - Multilayer Samples
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) by fusing various premanufactured specimens into one multilayer sample.
VCM discs 5 - 25 mm
Sample A
Sample B
Multilayer sample with distinct layers and sharp interfaces
The combination of a drug-loaded core with two diffusion barriers mimics the diffusion behavior of the well-known intra-vaginal birth control ring (IVR) from Merck Sharp and Dohme (NuvaRing™).
Avoid expensive process development and create comparable samples within one day. Get rid of pilot-scale experiments and obtain similar results by standard dissolution testing and surface corrections.
Our customers have written several publications in the field. Check out the publications page for more information about the IVR Screening of Implants.
For further development, VCM can be used to manufacture core-sheath structures. Embed a single implant concentric in a defined sheath in less than one hour.
Enclosed in sheath
Ø 2 mm
Formulation screening
Dissolution studies
Solid-state characterization
Mechanical characterization
Dissolution Studies
Perfect sample, comparable dissolution.
The drug release depends on material characteristics and the available surface area. Poor soluble drugs embedded in a polymeric carrier on a molecular basis are equipped with "spring and parachute" and achieve solubilities, orders of magnitudes higher compared to their crystalline forms.
Dissolution Testing
Paddle Apparatus
Intrinsic Dissolution
Stationary Disc
Intrinsic Dissolution
Rotary Disc
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. VCM specimens always have a defined surface without phase boundaries, unlike compacted tablets. The constant surface area will allow intrinsic dissolution-like release.
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.
VCM Sample
⌀ 8 mm - 150 mg
Stationary IDR Holder
According to Woods
MeltPrep offers a Woods conversion kit for your standard USP 2 tester (stationary and rotating mode). The IDR testing will enable a true 1D release for the most profound insights into the material behavior. It will also work for multilayer systems.
Microscopic Erosion Time Test (METT)
METT is a straightforward approach to ranking polymers for a specific API. A 50 mg ASD is embedded with the dissolution media between two glass covers. Using a microscope allows taking pictures of the VCM disc periodically and following the erosion.
Ø 10 mm
0,5 mm
50 mg
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. Click the button below to read the dedicated 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.
Formulation screening
Dissolution studies
Solid-state characterization
Mechanical characterization
Solid-State Characterization
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.
DSC Measurements
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. Read the dedicated publication to find more information on this topic.
Spectroscopy
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.
Formulation screening
Dissolution studies
Solid-state characterization
Mechanical characterization
Mechanical Characterization
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.
VS.
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%. Click on the button below to read the dedicated publication.
Study interactions between API and carrier. An API often significantly reduces melt viscosity (3000 to 5 Pas) and impacts processing conditions. Less than 1g (3x Ø8mm, 150mg each) gives access to processing temperatures and more. Read the more in the publication by clicking the button below.
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.
10x40 mm
VCM Bar Tool
Tensile Testing
VCM's newest tensile bar insert (ISO 37 Type 4) allows fast and easy sample preparation for tensile tests. It helps you to specify optimal materials, design parts to withstand application forces, and provide essential quality control checks for materials.
Conventional
Only 150 mg are required
Get rid of air inclusions or sample breakage. Use only 150 mg of material to prepare a homogeneous sample at the highest accuracy. Enjoy the ease of also releasing brittle materials and investigating isotropic samples. Start from powder or pellets and create the perfect tensile bars in less than 10 minutes.