Influence of API particle size and shape on flow and process induced attrition in a continuous direct compression work stream

The pharmaceutical industry is currently undergoing a paradigm shift with respect to manufacturing routes for oral solid dosage forms. Historically, the industry has utilised batch processes for tableting which have typically involved numerous, discrete, unit processes in trains (e.g. blending, granulation, milling and compaction). There may be gaps and material holds between these processes. In recent years, there has been a notable migration towards the utilisation of continuous manufacturing.

One consequence of continuous processing is that the input particle properties become significantly more important to enablement of the process. Ensuring that a material has properties which are suitable for feeding via a Loss in Weight (LIW) feeder in a controlled manner into a continuous blender are critical. Additionally, as the particle properties directly influence the ability of the process to reproducibly and efficiently deliver a suitable final dosage form, any change in the properties of the material during the process must be understood and/or controlled.

The objective is to study experimentally, the flow (feeder efficacy) and attrition behaviour of API particles with varying morphological nature within a continuous direct compression work stream. BMS also has a proprietary technology, co-processing, which improves the flow properties of materials, and may be a beneficial technology in enabling continuous direct compression.

The beneficiaries of the research and training of the CDT will be UK industry, the graduates of the programme, the wider academic community, and consumers :

(i) UK industry: the formulation sector is wide and diverse, and our industry partners are world-leading in a number of areas; foods (PepsiCo, Mondelez, Unilever), HPC (P+G, Unilever), fine chemicals (Johnson Matthey, Innospec), pharma (AstraZeneca, Pfizer, Imerys) and aerospace (Rolls-Royce). All projects are cocreated with industry, and cofunded - the majority will be EngD students based in company sites. Industry will benefit in a number of ways: (i) from a supply of trained graduates in this critical area, with > 90% of graduates of the programme to date getting jobs in formulation companies, and (ii) through participation in industry-academia research projects in which students work within the company on projects of practical value, (iii) through the synergy possible between companies in different non-competitive sectors (we have current projects between Mondelez and P+G, and Johnson Matthey and Unilever resulting from CDT linkages). We will also work with Catapult Centres, including the National Formulation Centre at CPI and the MTC at Coventry, to enhance the industry relevance of the CDT and train students in modern manufacturing methods.

(ii) Graduates of the programme: students are trained in a critical area where graduates are in short supply, obtain training and experience of the issues involved in industrial and collaborative research, present their work at external and internal meetings and get good jobs (>90% within formulation companies). Many of our graduates are now reaching senior positions in industry, and one, Dr Stewart Welch of Rolls Royce, is now the representative of Rolls-Royce on our Industrial Management Committee. In the next 5 years we will build at least 50 new projects with companies, creating EngD and PhD graduates, a new generation of leaders for the formulation industries.

(iii) Wider academic community in the UK and elsewhere. We will ensure that students on the programme write papers (as many as possible with industrial co-authors) on formulation projects. This is a vital part of the CDT, as it both ensures and demonstrates the academic quality of the programme. We have published extensively in areas such as; soft solid mixing processes (Unilever, Johnson Matthey; see Hall et al., Chem.Eng. Res. Des. 91, 2156-2168, 2013); food materials for enhanced mouthfeel, low-salt and low-sugar delivery, (Pepsico, Nestle, Mondelez; such as Moakes et al RSC Advances 5, 60786-60795, 2015); design of innovative cleaning strategies (Unilever, GSK, Heineken, P+G; Food Bioprod. Proc., 93, 269-282, 2015); characterisation of domestic cleaning processes (washing machines and dishwashers) to minimise water usage (P+G; Chem.Eng Sci., 75, 14, 2012); in-vitro models for formulated product breakdown and nutrient and drug delivery in the mouth, stomach and GI tract; EngD work followed up by BBSRC and industry funding (Eur J Nutr. 55, 2377-2388, 2016); dynamics of spray driers (P+G, AIChE J 61 1804-1821 2015; Chem. Eng. Sci. 162, 284-299, 2017), and ways to reduce waste in soyamilk production (Unilever; Innovative Food Science & Emerging Technologies, 41, 47-55, 2017).

(iv) consumers: many of the companies we work with are involved in Fast Moving Consumer Goods, where research has direct consumer benefit, for example in the creation of low fat foods that have high-fat mouthfeel. In addition, the overall aim of the programme is to develop sustainable formulated products and processes; such materials will be better for the environment and consumers.