Microfluidics technology for the formulation design and production of liposomal products

Student thesis: Doctoral Thesis

Abstract

In recent years, microfluidics technology has been researched as an alternative liposome manufacturing technique to improve batch-to-batch consistency and overall production costs. Whilst previous research has shown microfluidics parameters such as the flow rate ratio (FRR) adopted in the microfluidic process is important, there is a lack of defined operating parameters and designed space for liposome production. To this end, this thesis focuses on microfluidics technology for the production of a range of liposomal formulations containing proteins or small molecular drugs, as well as defining the optimal manufacturing parameters.Investigation of the microfluidics system shows the process is rapid and reliable, in comparison to traditional methods. For the first time through collective analysis, both the formulation composition and microfluidics manufacturing parameters were shown to impact liposomal characteristics. Analysis of the parameters (using design of experiments) allowed the identification of the design space with the ability to adjust microfluidics parameters to meet formulation specifications. In particular, a high FRR (3:1 FRR) and initial lipid concentration of above 3 mg/mL were shown to be the two most important factors when producing small homogenous liposomes (<100 nm). Also, a scalable manufacturing model was developed without the need for bespoke equipment, using readily available instruments.The model is able to manufacture liposomes in a single step, followed by purification of liposomes using tangential flow filtration. A key feature, shown for the first time is the ability to monitor the quality of the liposomes produced at-line (in real time). The model developed enables quality assurance, with problematic batches easily identified therefore reducing waste and improving the overall efficiency of the manufacturing process.Moreover, to the best of knowledge, the studies in this thesis are the first to show the production of protein loaded liposomes using microfluidics. Results show microfluidics technology is able to produce protein and drug loaded formulations without further downsizing requirements. The encapsulation of protein (approximately 34%) and drug loading (approximately 40%) is significantly (p
Date of Award1 May 2019
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorYvonne Perrie (Supervisor) & Paul Hoskisson (Supervisor)

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