Vacuum Compression Molding as sample preparation for thermal analysis of thermoplastic materials. Dr. Daniel Treffer, CEO and Founder STK Annual Meeting, May 15th 2018 Innovation in Thermal Analysis and Calorimetry 15.05.2018 STK Annual Meeting 2018 1
What is Vacuum Compression Molding? VCM Tool Perfect samples 15.05.2018 STK Annual Meeting 2018 2
How did it start? - Start with my phd in the field of pharmaceutical engineering at the Institute of Prof. Khinast in September 2011 - First contact with hot-melt extrusion. Measurement of material properties. Problems 1. Bubbles Kollidon VA64 HPMCAS 2. Degradation 3. Shrinkage e.g. Rheo Data 4. Sticking Soluplus Kollidon VA64 Reproducible measurements are impossible! 15.05.2018 STK Annual Meeting 2018 3
The light-bulb moment 13. February 2014 The hands on experience of a new material Teflon foil reinforced with glass-fibres 15.05.2018 STK Annual Meeting 2018 4
Introduction Video https://youtu.be/fz1p9hu526q 15.05.2018 STK Annual Meeting 2018 5
What are the innovations? Compaction pressure (vacuum) Movable piston VCM Insert Solidifying #1 Adaptable sample chamber Powder or flakes etc. Geometrically defined sample, no voids or bubbles Front foils #2 Peelable sample chamber 15.05.2018 STK Annual Meeting 2018 6
VCM Essentials Vacuum Unit 0,1 mbar 1 atm Heating Unit 300 C 25 C Cooling Unit SLOW & FAST 15.05.2018 STK Annual Meeting 2018 7
Flawless Samples Rotate them www.meltprep.com/spinners 15.05.2018 STK Annual Meeting 2018 8
Applications Solubility Surface Tension Rheology Diffusion Hardness Notch Impact Strength Density Dynamic Mechanical Analysis Stability Thermal Conductivity Dissolution Heat Capacity Spectroscopy 15.05.2018 STK Annual Meeting 2018 9
Complex Viscosity (Pas) Rheology (Discs 8-25 mm) Shear Flow 10 5 10 4 Soluplus homogenous with bubbles 10 3 10 2 10-2 Conventional Increased accuarcy with VCM Treffer et al. 2015 0.1 1 10 Shear Rate (s -1 ) 140 C 150 C 160 C 100 15.05.2018 STK Annual Meeting 2018 10
Extensional Viscosity (Pas) Rheology (Bars 10x40 mm) Extensional Flow Homogeneous 10 7 10 6 10 4 Soluplus Conventional 25s -1 10s -15s-1 3s -1 1s -1 New insights via VCM Strain Hardening 0.3s -1 0.03s -1 with bubbles early rupture 10 5 10 3 10-3 10-2 Trouton Ratio 0.1 1 10 100 Time [s] 15.05.2018 STK Annual Meeting 2018 11
mdsc Signal DSC Measurements (Discs 5 mm) powder powder too noisy 1st heating VCM sample HPMCAS VCM Troiss et al. 2017 T G = 145 C DSC crucible 0 Temperature ( C) 200 15.05.2018 STK Annual Meeting 2018 12
Heat capacity (J/kgK) Conductivity (W/mK) DSC Measurements (Discs 5 mm) 2500 0.4 Thermal Conductivity via DSC Soluplus 2 Samples Thicknesses mdsc and Math 0.4 mm 3 mm Troiss (2017) 500 0 50 100 150 0 200 Temperature ( C) 15.05.2018 STK Annual Meeting 2018 13
Diffusion Rate (µg/day) Formulation Screening (Multilayer Systems) (Discs 5-25mm) IVR e.g. Ø 50 mm $761 m Merck & Co Cross Section Drug loaded core Diffusion Barrier 60 30 VCM multilayer prototype Co-extruded version Diffusion Barrier Drug Loaded Core 100 µm 4 mm 100 µm Lateral surface sealed with barrier glue. 0 Eder et al. 2017 0 5 10 15 20 Time (days) Diffusion Barrier 15.05.2018 STK Annual Meeting 2018 14
Intensity (counts) Formulation Screening (ASD Stability) Testing of ASD stability after 1, respectively 4 weeks of storage at accelerated conditions (40 C and 75% RH) via DSC and WAXS VCM prepared from cryo milled blend shows small melting endotherm in first heating 10% API + 90% Eudragit E (4 weeks) 10% API + 90% Eudragit E (1 week) 10% API + 90% Eudragit E Eudragit E 2θ API 15.05.2018 STK Annual Meeting 2018 15
Released Fenofibrate [%] Released Fenofibrate [%] Formulation Screening (Dissolution Testing) Tablets with defined geometries. 120 100 80 0 Order 120 100 80 1 Order 60 60 40 40 20 20 0 0 30 60 90 120 Time [min] 0 0 30 60 90 120 Time [min] 15.05.2018 STK Annual Meeting 2018 16
Released Fenofibrate [%] Released Fenofibrate [%] Formulation Screening (Dissolution Testing) Tablets with defined geometries. 120 100 80 0 Order 120 100 80 1 Order 60 60 40 40 20 20 0 0 30 60 90 120 Time [min] 0 0 30 60 90 120 Time [min] 15.05.2018 STK Annual Meeting 2018 17
Applications 15.05.2018 STK Annual Meeting 2018 18
NOWHERE NOW HERE A little change can make a big difference. 15.05.2018 STK Annual Meeting 2018 19
Contact 15.05.2018 STK Annual Meeting 2018 20