Applications of VCM

Versatile as a Swiss-army knife.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.