Centre for Pharmaceutical Engineering Science (CPES) “Innovation through Focused Interdisciplinary Research” Professor Anant Paradkar http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Heritage in Pharmaceutical Engineering 1994 Bradford Particle Design Ltd established as a spin-out from the School of Pharmacy 2001-Bradford Particle Design sold to Nektar Therapeutics for $200 million 2003-Institute of Pharmaceutical Innovation (IPI) opens incorporating the University Analytical Centre 2010-Centre for Pharmaceutical Engineering Science established at UoB CPES is an interdisciplinary research centre, which has been developed across the pharmaceutical sciences, polymer and process engineering disciplines. CPES offers research based solutions in the areas of pharmaceutical materials, drug delivery systems, process innovations, material characterisation and Process Analytical Technology (PAT). http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Working with us..... Project Delivery Dedicated Project Teams and Managers Access to a range of sophisticated equipment Engage with academic experts UoB Legal and Contracts Team Projecting timelines using Gantt charts and active tracking of the projects. Weekly meetings on project updates. Commercial Focus Differentiated Contract Research Novel Processing Technologies Patented Technologies for out-licensing Mechanism of Engagement Contract Research-Fee for Service Collaborative Research Shared IP- Grant Funded Projects Studentships and Knowledge Transfer Partnerships Industry Sectors Pharmaceuticals Healthcare Nutraceuticals Process Manufacturing Industries http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Core Capabilities and Areas of Expertise Preformulation Studies Solid State Engineering Thermal Analysis Solubility & Dissolution (USP II and USP IV) Solution State Stability & Method Development Stability Studies Solid State Screening Process Development & Optimisation Hot Melt Extrusion (HME) Spray and Freeze drying Particle Size optimization Processes Injection and Micro-moulding Innovative Technologies Effervescent Formulations Abuse Resistant Systems (ARS) Solvent Free co-crystallization Novel Microneedles Green Technologies Process Analytical Technology & QbD NIR/Raman in-line analysis HME FBRM/Microscopy Crystallisation Design of Experiments QbD focused product development & process optimization Pharmaceutical Formulation Development Poorly Soluble Drugs Transdermal Delivery Inhaled Therapeutics Conventional Dosage Forms http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

A Model Approach to API Development Drug Literature & patent review/ strategy development Primary screening Process development & optimization with in-line monitoring Stability studies and pre-clinical manufacturing Screening techniques -solution -grinding -hot-stage -microwave -slurry Screening -Amorphous Polymorph Hydrate Co-crystal Salt screen Artemisinin API Processes HME Ultrasound - Microwave Slurry Crystallization Solution Crystallization Freeze drying Spray drying. In-line tools -NIR -Raman -FBRM -PVM -Ultrasound -Rheology measurement CBZ API Supporting Analytics -X-Ray Diffraction -Thermal Analysis -Particle Characterisation -Raman Microscopy -UHPLC -Surface energy analysis http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Case Study 1 – Co-crystal screening for isostructural compounds CEPS developed 2 novel stable co-crystals for a client. Co-crystal screening was performed using the state of the art equipment coupled with high-end analytics. Structure was determined using Accelerys software. New crystal phase with coformer 1 Characterisation techniques Compound A Screening techniques used New crystal phase with coformer 2 PXRD DSC Raman IR Single crystal XRD Equilibrium solubility Intrensic Dissolution Ball milling Thermo-kinetic screening Microwave assisted slurry screening Compound B New crystal phase with coformer 1 http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Case Study 2 –Commercialisation of Novel technologies Solvent-Free Continuous Co-crystallisation (SFCC) CPES developed a solvent free continuous co-crystallisation technology. PCT Patent Application. A scalable and PAT enabled technology that produces co-crystals with novel physical characteristics. Active Pharmaceutical Ingredient (API) Co-former Co-crystal Tablets Tableting GB Patent Application No: GB 0813709.3 PCT Patent Application No: PCT/GB2009/050924 Co-crystals obtained by SFCC Licensing agreement negotiated with a UK based Pharmaceutical client. http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

A Model Approach to Formulation Development Drug Literature review/ Strategy development Feasibility studies Process selection, development & optimization with in-line monitoring Stability studies & pre-clinical manufacturing Pre-formulation -Physico-chemical characterisation -Solid-state & solution stability -Excipient selection -Excipient Compatibility Pellets Formulations -Conventional Dosage Forms -Melt extrudates & Moulded systems -Transdermal patches -Liquid crystal gels -Nano-suspensions -DPIs/pMDIs -Injectables -Lyophilised products Processing Options -Hot Melt Extrusion -Spray & Freeze Drying -Injection-moulding -Micro-moulding -Micronisation -Nanoprocessing -Granulation -SCF Crystallisation Transdermal Patches Moulded Tabs http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

CPES Technologies -Effervescent formulation Challenges with effervescent formulations Low humidity requirements (10-20%RH) Cost associated with controlled Thermo-hygrometric conditions High packing cost High compression force for tabletting Instability during processing and storage CPES approach (GB Patent – 20080083) Reduction in dehumidification cost Reduction in packaging cost Conventional processing Cost effective manufacturing Improved product stability Applications in wide sectors http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

CPES Technologies -Abuse Resistant System Bioavailability screening Abuse resistant pellet formulation ARS technology platform uses unique polymeric mixture processed to achieve desired properties Drug release can be customized by changing pellet size and polymer combination Hard pellet completely resistant to crushing Flexibility of dosage form Before dissolution After dissolution Oxycodone HCl ARS Formulation comparison study Test CPES ARS ARS_US771707 450ml of disso media (0.1N HCl) in 15 min 13.67% 15.9% 450ml disso media (0.1N HCl) in 15 min pretreated with 40% alcohol 16.5% 27.8% 450ml disso media (0.1N HCl) in 15 min pretreated with vegetable cooking oil 6.6% 12% 5ml water boiled and cooled, filtered 9.23% 2.1% Bioavailability screening 450ml disso (H2O) by 12 hr 100% 107.3% http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Case Study 3-Successful reformulation of a natural product for the export market Client :UK based SME. Challenge: To enhance the solubility and improve the odour of a natural product formulation. Outcome: A technology for water soluble and de-odourised material was developed allowing for easy formulation in a number of ways, liquid, gel and bio-adhesive patch. Patent filed and technology transferred. De-odourised product launched in overseas market. Timelines: 6 months. Problem Solving: A novel and patentable technology was developed. Relationship: A strong relationship was developed with the client which involved a number of follow-on projects and a Knowledge Transfer Partnership was established. WATER SOLUBLE PROPOLIS NOW AVAILABLE IN THE KOREAN MARKET PROPOLIS GEL PROPOLIS PATCH http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Case Study 4-Succesful reformulation of an unstable topical product containing a strong oxidizing agent Client : European based SME. Challenge: To reformulate a topical formulation which had poor stability due to the presence of an oxidising agent. Outcome: A simple process was developed which did not require organic solvent, complex equipment and made technology transfer much easier and gave a product that had no stability issues. Progressed to IP protection and preclinical trials. Timelines: 4 months Problem Solving: A number of approaches where investigated including microencapsulation before a novel liquid crystal phase formulation was developed. Flexibility: Constant review and communication with client to modify and shift the project focus as necessary. http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Case Study 5 -Development of injection moulded pharmaceutical dosage forms- Ibuprofen Process Current Approaches : Mould design optimisation Avoid compounding step Minimise residence time Challenges : Dissolution of tablet - Density Wastage - Runner system Thermal stability - Residence time Ibuprofen + HPMCAS-LF Injection moulding http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Case Study 6-Identification of the problem and reformulation of a commercial product Client : European based SME. Challenge: To reformulate a commercial product with bioadhesivity and irritation problems. Outcome: New technology was developed exploiting the fundamentals of crystallisation and precipitation which enabled the preparation of an irritant free formulation. Scale-up and product performance trials in human volunteers and a patent application followed. Timelines: 9 months. Problem Solving: Investigations focused on the root cause of the problems with the aim of understanding of the fundamental processes, with this information it was then possible to resolve the issues allowing successful reformulation of the product. Costing: The original pricing was maintained over the 9 months project. http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Sichuan University, Chengdu Processing Sichuan University, Chengdu Changchun University Of Science and Technology Green Processing ICT, Mumbai Technologies NCL, Pune Shanghai Institute Of Materia Medica Beijing University Of Chemical Technology UKIERI Trilateral Research Partnership   UK-China team CPES team with ICT http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/

Contact: Dr. Jason R. Jones Commercial Manager +44 (0)1274 236193 j.r.jones@bradford.ac.uk http://www.pharmaceuticalengineering.brad.ac.uk/ http://www.bradford.ac.uk/research/rkt-centres/pharmaceutical-engineering/