Spray Drying as a One-Step Formulation Process

Micro Spray Drying as a One Step Formulation Process
The manufacture of tailored drugs for small numbers of patients (where n could be =1) is challenging both technically and economically. The large-scale manufacture of solid dispersions is multi-stage and inefficient. Additive manufacturing offers one solution to the manufacture of single tailored dosage form but can suffer from often requiring specialized inks that maybe specific to each therapeutic. Such can limit its ability to rapidly prototype and explore formulation-space, and moreover creates significant issues and barriers to regulatory approval.
The spray drying process is a long-established, approved continuous manufacturing process that is routinely used for the production of amorphous solid dispersions, used to enhance the oral bioavailability of poorly soluble drugs. The concept here is to scale down the spray drying process to the point of being able to produce amorphous solid dispersions for a single dosage unit at a time, together with the any other constituents necessary for the dosage form.
This could be run at a manufacturing scale, producing many dosage forms individually in a single step, where 7 or more steps are currently required. Or, this could be run at a small scale, producing personalised tablets of poorly soluble drugs on demand.
Spray-drying is favoured here as it is known to be a highly controllable and repeatable process, hence it is ideally suited to:
- SCALE UP for rapid single step manufacture of complex tablets.
- SCALE DOWN to enable personalised tablet manufacture.
The project will develop a flexible miniaturised spray drying manufacturing process platform for small quantities of patients offering the capability to manufacture tailored micro-encapsulated powder, for use in oral dosage forms such as capsules, incorporation into micro needle arrays, blending with proteins, etc.
We will study the engineering and physical principles behind the spray-drying process, in particular using physicochemical characterization of properties such as surface tension and viscosity to reveal how these can inform the design and engineering of the fluidic (micro and macro) flow, nozzle geometry, gas flow, temperature, flow geometry, etc. We will design and develop a working miniaturized spray-drying prototype and use this and the knowledge gained from the characterization of the materials and their behaviour in the device to generate design rules that can be used to formulate personalized dosage forms of a variety of APIs. Micro-spray dried material will be compared to that produced using a traditional small-scale manufacture system.
One potential application for our flexible micro-spray drying platform would be for personalised combination chemotherapy. Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. The ability to potentially formulate, on site and on demand, personalized combination therapies offers saving in cost and time, and stands to make a significant impact in the delivery of therapies.
Rapid small-scale manufacture would also quicken the development of new formulations, either for new actives or for new indications.

Project aligned to Pharmaceutical Process Engineering and Advanced Product Design

Pharmaceutical technologies underpin healthcare product development. Medicinal products are becoming increasingly complex, and while the next generation of research scientists in the life- and pharmaceutical sciences will require high competency in at least one scientific discipline, they will also need to be trained differently than the current generation. Future research leaders need to be equipped with the skills required to lead innovation and change, and to work in, and connect concepts across diverse scientific disciplines and environments. This CDT will train PhD scientists in cross-disciplinary areas central to the pharmaceutical, healthcare and life sciences sectors, whilst generating impactful research in these fields. The CDT outputs will benefit the pharmaceutical and healthcare sectors and will underpin EPSRC call priorities in the development of low molecular weight molecules and biologics into high value products.

Benefits of cohort research training: The CDT's most direct beneficiaries will be the graduates themselves. They will develop cross-disciplinary scientific knowledge and expertise, and receive comprehensive soft skills training. This will render them highly employable in R&D in the pharmaceutical, healthcare and wider life-sciences sectors, as is evidenced by the employment record in R&D intensive jobs of graduates from our predecessor CDTs. Our students will graduate into a supportive network of alumni, academic, and industrial scientists, aiding them to advance their professional careers.

Benefits to industry: The pharmaceutical sector is a key part of the UK economy, and for its future success and international competitiveness a skilled workforce is needed. In particular, it urgently needs scientists trained to develop medicines from emerging classes of advanced active molecules, which have formulation requirements that are very different from current drugs. The CDT will make a considerable impact by delivering a highly educated and skilled cohort of PhD graduates. Our industrial partners include big pharma, SMEs, CROs, CMOs, CMDOs and start-up incubators, ensuring that CDT training is informed by, and our students exposed to research drivers in, a wide cross-section of industry. Research projects in the CDT will be designed through a collaborative industry-academia innovation process, bringing direct benefits to the companies involved, and will help to accelerate adoption of new science and approaches in the medicines development. Benefit to industry will also be though potential generation of IP-protected inventions in e.g. formulation materials and/or excipients with specific functionalities, new classes of drug carriers/formulations or new in vitro disease models. Both universities have proven track records in IP generation and exploitation. Given the value added by the pharma industry to the UK economy ('development and manufacture of pharmaceuticals', contributes £15.7bn in GVA to the UK economy, and supports ~312,000 jobs), the economic impacts of high-level PhD training in this area are manifest.

Benefits to society: The CDT's research into the development of new medical products will, in the longer term, deliver potent new therapies for patients globally. In particular, the ability to translate new active molecules into medicines will realise their potential to transform patient treatments for a wide spectrum of diseases including those that are increasing in prevalence in our ageing population, such as cardiovascular (e.g. hypertension), oncology (e.g. blood cancers), and central nervous system (e.g. Alzheimer's) disorders. These new medicines will also have major economic benefits to the UK. The CDT will furthermore proactively undertake public engagement activities, and will also work with patient groups both to expose the public to our work and to foster excitement in those studying science at school and inspire the next generation of research scientists.