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SSPC Impact Case Study: Health

SSPC Impact Case Study: Small Molecule

SSPC Impact Case Study: Sustainability

US-Ireland Centre-to-Centre nanoparticle partnership

Project Partner:

University of Limerick, Queen’s University Belfast, Purdue University, Rutgers

Areas of Impact:

Economic, Health, Societal

Scientific Domains:

Small Molecule / Drug Product

The US-Ireland Centre-to-Centre Partnership: Partnership in Continuous Manufacturing for Nano-based Drug Products (C2C)

Project 1 leads: Luis Padrela, Kevin Ryan, University of Limerick, Rohit Ramachanddran, Rutgers
Project 2 leads: Kieran Hodnett, Sarah Hudson, University of Limerick, Gavin Andrew, Queens
Project 3 leads: Gavin Walker, Denise Croker, University of Limerick

The tripartite US-Ireland R&D partnership project titled ‘Partnership in continuous manufacturing for nano-based drug products links together three of the world’s significant research centres in pharmaceutical manufacturing: (SSPC) located at University of Limerick, Ireland; The Center for Structured Organic Particulate Systems (C-SOPS) at Purdue University and Rutgers University, USA; and The Centre for Pharmaceutical Sciences (CPS) at Queens University Belfast.

The alliance builds on the combination of expertise of these three centres: SSPC for upstream continuous processing for drug synthesis and crystallisation; CSOPS for continuous drug product manufacture; and MPRI for polymers for drug delivery. The project will be funded by Science Foundation Ireland in Ireland; the National Science Foundation (NSF) in the US; and the Department of Employment and Learning Northern Ireland (DEL/NI) in the UK.

Research Objectives
The overarching goal of the proposed collaboration is to fuse the capabilities and resources of three significant international centres with the goal of establishing and delivering new end to end continuous manufacturing capabilities for poorly soluble micron and nanosized APIs (Active Pharmaceutical Ingredients) that will transform the global supply chain for medicines by developing techniques capable of:

(1) Making nano-particulate active pharmaceutical ingredients
(2) Retaining their desirable nano properties throughout the entire manufacturing chain.

The Projects
The US-Ireland C2C project is organised into three distinct research projects namely:

  • 1: A novel spray drying process for the continuous generation and drying of nanoparticles using supercritical methods
  • 2: Continuous heterogeneous crystallization of APIs in and onto excipients
  • 3: Continuous manufacture of co-crystal APIs using in-line Raman spectroscopy

Goals and strategy
Project 1 aimed to develop supercritical CO2 methods such as the Supercritical Enhanced Atomization (SEA) and Gas Antisolvent (GAS) to improve the solubility of pharmaceutical materials. Specifically, this project aims to generate nanoparticles of Active Pharmaceutical Ingredients (APIs) using a continuous process such as the SEA method. This work also aims to collaborate with an international research group in Rutgers University to develop a population balance model for batch and continuous supercritical methods. Finally, the primary objective of this work is to highlight that the implementation of this technology on existing pharmaceutical spray dryers is possible and will provide a new tool for targeting the nanoscale and enhancing the solid-state form involved in pharmaceutical manufacturing.

Project 2 aimed to prepare, stabilize and isolate poorly water-soluble BCS class II Active Pharmaceutical Ingredients (APIs) nanoparticles in solid-state with the help of Montmorillonite (MMT) clay as carrier particles in a batch as well as a continuous process in order to enhance the dissolution rate, hence bioavailability of these APIs. The strategy of the project includes the production of these nanoparticles in suspension using a reverse antisolvent precipitation technique in the presence of ‘as received’ MMT carrier particles (~30 mm) and/or MMT carrier particles whose surface had been slightly modified with a cationic protein, protamine sulphate salt (PA). The resulting nanoparticle adsorbed onto carrier particles can be isolated directly from suspension into a solid-state form by simple filtration followed by air-drying.

Project 3 aimed to develop novel scalable continuous extrusion processing for the manufacture of co-crystal drug products and to implement advanced process analytical technologies, i.e. Raman, to develop a mechanistic understanding of how formulation and process factors affect co-crystal performance. To do this a Design of Experiment (DoE) approach has been taken to study the effect of different process parameters on cocrystallization and defining the optimised formulation and the mechanical properties like tabletability, compressibility and compactibility of optimised formulation were subsequently studied.

Outputs and Achievements
During the C2C award:

  • 1 patent awarded (US Patent no. 10849989, European Patent Application No. 17784551.8)
  • NSF/SFI I-Corps Innovation Corps 2016
  • Enterprise Ireland Commercialization Fund 2017

Funding leveraged after the C2C award

  • Science Foundation Ireland FFP 2019
  • Enterprise Ireland Feasibility Grant 2020
  • Enterprise Ireland Comm Fund 2021
  • SFI Research Infrastructure NaPRO 2021

Peer-reviewed publications

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