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Solvent-free Manufacturing of Liposomes with High Drug Encapsulation

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


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.


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.


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.


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

  • swapnil2010, 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


Carla B. Roces, Rachel Donaghey and Yvonne Perrie, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom

Yang Su, Microfluidics International Corporation, Westwood, Massachusetts, 02090, United States

Acknowledgments: Microfluidics International Corporation, Westwood, Massachusetts, 02090, United States, provided M110P Microfluidizer processor.

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Posted by

Matt Baumber


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