On Tuesday, June 30, 7:00am - 9:00am EST, The Microfluidics team was pleased to present during the virtual meeting of the upcoming Controlled Release Society Annual Meeting.
Technical session 3: New Approaches to Physicochemical Characterization, Scale-up and Stability Measurements
Abstract
Introduction: A major drawback of manufacturing processes for liposomes is the use of an enormous amount of solvents during manufacturing. In this study, we have investigated a manufacturing method for drug-loaded liposomes without any solvents using the electric benchtop laboratory M110P Microfluidizer® processor that requires no compressed air and no hydraulic cooling water to achieve up to 30,000 psi operating pressure produces product flow rate up to 120 mL/min with guaranteed scalability.
Methods
Manufacturing of doxorubicin-loaded liposomes: Liposomes were prepared by mixing powdered distearoyl phosphocholine and SyntheChol® with/without distearoyl phosphoethanolamine methoxy(polyethylene glycol)-2000 with 100 mL of hydration buffer at 70°C. Lipid dispersion was high shear mixed at 4000 rpm for 1 h at 70°C. Liposomes were size reduced at 65-70°C using Microfluidizer® processor (Massachusetts, USA). The formulations were processed at pressures of 5000 - 20000 psi and number of passes ranging from 1 to 3. Formulations were subjected to tangential flow filtration for buffer exchange followed by the addition of doxorubicin and incubated at 60°C for 15 mins.
Manufacturing of amphotericin B-loaded liposomes: Acidic succinate buffer with sucrose was heated at 70°C using a water bath. Distearoyl phospho glycerol (DSPG) was added to the buffer. Basic amphotericin B solution was prepared using 2M sodium hydroxide. Amphotericin B solution was added to the acidified DSPG suspension at 70°C. DSPG-Amphotericin B suspension at pH 5.5 was high shear mixed for 1 h at 70°C with powdered hydrogenated phosphatidylcholine and SyntheChol®. Liposomes were size reduced at 65-70°C using Microfluidizer® processor.
Results
Empty liposomes formulations were optimized at 15-20k psi with three passes produced liposomes which were 85-101 nm in particle size and 0.20 PDI. Doxorubicin-loaded PEGylated liposomes can be manufactured using 18k psi pressure with 107 nm particle size, 0.19 PDI at pass 2 and 98 nm particle size, 0.16 PDI at pass 3. Doxorubicin loading was unaffected by the number of passes achieving 97-98 % drug entrapment. The Non-PEGylated liposomal formulation showed 105 nm particle size and 0.23 PDI at pass 3 with 18k pressure. Additionally, amphotericin B-loaded liposomes were prepared at 20k psi offering 104 nm, 0.26 PDI and 100 % drug loading. Sterilization by filtration showed no changes in liposomes size, PDI and drug loading.
Conclusion
In conclusion, a new method for the production of liposomes has the potential to manufacture liposomes at a large scale without using solvents resulting in uniform particle size distribution and high drug loading.
Presenter Biography
2010, Bachelor of Pharmacy, University of Pune, India- 2012, Masters degree in Drug Delivery (Pharmaceutics), University College London, London.
- 2014, Research scientist (Drug delivery), University College London, London.
- 2015, PhD in drug delivery, Aston University, Birmingham.
- 2017, Post-Doc and contract formulation development researcher at University for Strathclyde.
- 2019, Pharmaceutical Formulation Development Specialist at University of Strathclyde, Glasgow and Lonza, Edinburgh.
- Currently, Formulation Program Manager, BDD Pharma, Glasgow
Co-Authors:
Carla B. Roces, Rachel Donaghey and Yvonne Perrie, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Yang Su, Microfluidics™, Westwood, Massachusetts, 02090, United States
Acknowledgments: Microfluidics™, Westwood, Massachusetts, 02090, United States, provided M110P Microfluidizer processor.
