Microfluidics technology for the formulation design and production of liposomal products

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<0.05) more than formulations produced by thin film lipid hydration followed by sonication. Analytical methods to quantify encapsulation of protein were developed; the results from the two different quantification approaches were equally comparable. The quantification methods are efficient and reliable, allowing for rapid screening of liposomal formulations. In addition, the stability and characteristics of the liposomes was preserved by developing a high-throughput freeze drying method using 96 well plates. In conclusion, the results from this thesis indicate microfluidics technology is a viable option for the production of a vast range of liposomal formulations for therapeutic use.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2019

Author dc:creator

• Hussain, Maryam Tabassum

Advisor dc:contributor.advisor

• Perrie, Yvonne

DOI

10.48730/mamd-9088

Identifier

T15311

Author Identifier

201673917

OAI identifier oai:identifier

oai:strathclyde:wh246s22h