Dr Claire MacDonald Business Development Manager CMAC National Facility

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1 Dr Claire MacDonald Business Development Manager CMAC National Facility

2 This presentation will cover CMAC Overall Vision CMAC National Facility Capabilities and Expertise API Process Development Secondary Formulation Advanced Analytical Services Ways of working with CMAC National Facility

3 EPSRC Future Manufacturing Research Hub in Continuous Manufacturing and Advanced Crystallisation Vision: To deliver predictive design tools and novel integrated continuous processing platforms for the supply of next generation high performance personalised products. World Research Class Facilities World Training Class & Facility Skills Training Translation & Skills to Industry Translation to Industry Productive partnerships driven by a collaborative, international outlook and regulator engagement Co-created with industry to address key manufacturing challenges and skills needs

4 NATIONAL FACILITY Continuous Manufacturing and Advanced Crystallisation National Research Facility Dedicated technical support within World Class Manufacturing Research Facility Unique expertise in advanced crystallisation, process development, formulation and product analysis Continuous process skids for process development, state-of-the-art analysis and characterisation capabilities and a comprehensive suite of PAT tools

5 CAPABILITIES & EXPERTISE Primary Processing Crystallisation platforms covering batch and continuous methods e.g. cooling, anti-solvent, reactive and evaporative crystallisation Secondary Processing Formulation platforms investigating solid oral dosage forms e.g. extrusion, blending, compaction and milling PAT/Spectroscopy Process monitoring technologies and off-line benchtop spectroscopy techniques e.g. FBRM, PVM, Raman, IR, UV-Vis Imaging Visualisation using a variety of microscopes e.g. optical, SEM, AFM and nanoscale computed tomography X-Ray Diffraction Powder, single crystal, and small angle X-ray scattering (SAXS/WAXS) for understanding molecular structure Materials Characterisation Techniques to understand the physical properties of solid powders and tablets e.g. BET, porosity, pyncometry, surface energy, vapour sorption, density, dissolution, solubility

6 Crystal density % volume density % API PROCESS DEVELOPMENT Crystallisation platforms covering batch and continuous methods including cooling, anti-solvent, reactive and evaporative crystallisation Continuous Crystallisation Case Study 5 days continuous operation (no fouling) 26% increase in yield (vs batch) Significant reduction in particle size distribution span vs stirred tank reactor Reduction in process time from (16h to 5h) Batch to continuous methodology adopted Advanced process control Dial a Particle capability size µm 100 batch STR COBC crystal size µm

7 SECONDARY FORMULATION Secondary Processing Formulation platforms investigating the manufacture of solid oral dosage forms e.g. hot melt extrusion, blending, compaction and milling to enhance the bioavailability of solid dose forms Examples of projects conducted within the facility; Twin Screw Extrusion Investigation and Process Optimisation in a manufacturing setting Spray Drying viability studies including initial assessment/characterisation of current commercial product and product isolation feasibility study Improve process understanding of shear effects on particle properties in twin screw granulation

8 Hot Melt Extrusion (HME) Overview SECONDARY FORMULATION Manufacture of solid solutions, dispersions to enhance bioavailability of solid dose forms Determination of operating space (shear, temp) Formulate API loaded filaments by HME and 3D printing to tailor attributes such as dissolution performance 8

9 ADVANCED ANAYLTICAL SERVICES Materials Characterisation Techniques to understand the physical properties of solid powders and tablets e.g BET, porosity, surface energy, vapour sorption, density, solubility

10 Methods to study crystal shape and size Microscopy: Optical (mm-μm) Scanning Electron Microscopy SEM (hundreds μm-nm) Atomic Force Microscopy AFM (μm-nm) ADVANCED ANAYLTICAL SERVICES Scanning Electron Microscopy Optical Microscopy Atomic Force Microscopy 10 μm

11 ADVANCED ANAYLTICAL SERVICES Malvern Morphologi G3 FBRM (focus bean reflectance measurement) PVM (particle vision measurement) Particle Sizing Technique Selection & Method Development Process Analytical Technology implementation - advise on the appropriate technique selection and implementation for direct process control and monitoring

12 ADVANCED ANAYLTICAL SERVICES Nano Tomography Bruker NanoCT (SkyScan 2211) Solid compounds, devices/components, pastes & gels Best suited for : Non-invasive, threedimensional structural imaging of solids. Can be applied to analyse for samples with sizes > ca. 20 µm. Examples Root cause investigation of batch to batch variability commercial products Surface analysis and API distribution studies in final product/tablet

13 IMPACT CASE STUDIES Collaborative project with AZ Dial a particle Model Predictive Control Reduced particle size and improved control on lactose Use of CMAC seeding approach Installed in Basel continuous plant Continuous crystallisation feasibility Learning applied to batch process Debottlenecked $1bn fungicide Beta testing and characterisation of novel equipment. InnovateUK, GSK CPHI Barcelona

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15 WORK WITH US Research and Development Contract Research Analytical Service Consultancy Service We work with both large and small companies to deliver research Through working with the National Facility Team we can apply our research expertise to support industry during both early product development phases to fully commercialised product manufacturing.

16 Contact the CMAC National Facility Team with your enquiries