Liposomes Meet Fluidized Bed: From Lipid Vesicles to Solid Dosage for Liposomal Drug Delivery

This poster has been presented at the  15th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology  which took place in Prague, Czech Republic.

Liposomes Meet Fluidized Bed: From Lipid Vesicles to Solid Dosage for Liposomal Drug Delivery

INTRODUCTION

• Liposomes are versatile nanocarriers capable of encapsulating both hydrophilic and lipophilic drugs[1], offering controlled release and improved bioavailability. Despite their therapeutic potential, conventional liposomal formulations are predominantly produced and stored as aqueous dispersions, which often suffer from limited physical and chemical stability[2], high storage and transport costs, and short shelf life. Transforming liposomal suspensions into solid dosage forms represents a promising strategy to overcome these limitations and facilitate patient-friendly administration routes.
• Fluid bed processing, including drug layering and granulation techniques, provides a scalable and continuous approach to convert liquid liposomal dispersions into dry, free-flowing granules or coated particles, while preserving the integrity of the vesicular structures. Unlike freeze-drying or spray-drying, the fluid bed process allows gentle drying under controlled conditions, with the potential to directly integrate liposomes into solid oral or inhalable dosage forms.
• This study explores the feasibility of applying fluid bed techniques for liposomal drug delivery systems. By selecting suitable excipients as protectants during the fluid bed processing and optimizing both formulation parameters and process conditions, the work aims to bridge the gap between liquid liposome preparation and solid dosage manufacturing by using fluid bed processing, paving the way for efficient and scalable liposomal drug delivery products.

Production of liposomes

• Liposomes composed of Soy phosphatidylcholine (SoyPC) with and without cholesterol (Chol) and Polyethylene Glycol (PEG) were prepared using FR-JET® technology (Leon-Nanodrugs, Germany)
• FR-JET® reactor: 2 mm mixing chamber diameter (pinhole combination: 200 μm aqueous phase inlet, 100 μm organic phase inlet), total flow rate (TFR): 80 mL/min, flow rate ratio (FRR): 2:1 (aqueous: organic)
• The liposomes were dialyzed overnight against 10 mM phosphate buffer (PBS 7.4) Dialyzed samples were filtered using polyethersulfone (PES) filters with a pore size of 0.22 μm[3]

• Kollidon® VA 64 (copolymer of vinylpyrrolidone–vinyl acetate; KVA) was used as protectant for liposomes as well as binder for the fluid bed process (5% concentration in the liposome suspension)
• Drug layering was performed using a fluid bed bottom-spray process using a Mini-Glatt equipped with a Microkit (Glatt GmbH, Germany)
• 20 g of Microcrystalline Cellulose (MCC) spheres (CELLETS® 500) were used as the solid starting cores

Characterisation

• The particle size distribution of the liposome-loaded pellets was analyzed using the Eyecon2 system (InnoPharma Technology, Ireland)
• The redispersibility of liposomes from the pellets was tested by adding demineralized water and analyzing the particle size by dynamic light scattering (DLS) using a Zetasizer® (Malvern Panalytical Ltd., UK)
• The size of the redispersed liposomes was compared to the original liposome formulation

RESULTS AND DISCUSSION

• Fluid bed processing was conducted by spraying either PBS buffer, liposome suspension without KVA as protectant, or liposome suspension with KVA as protectant. The same process parameters (e. g. inlet air temperature, atomizing air pressure) were used in all experiments to ensure that any observed differences could be attributed solely to the presence or absence of liposomes or/and KVA. The particle size and size distribution of the liposome-loaded pellets, as well as the redispersed liposomes from pellets, were measured and compared with negative controls.
• Redispersibility of liposomes from dried pellets: The redispersibility is a critical quality attribute of the final liposome-loaded products. Three weeks after production, z-average-values of 62 – 64 nm for both, the SoyPC and SoyPC/Chol/PEG liposomes, and respective PDI values of 0.24 and 0.29 were measured (Figure 2). For the liposomal loaded pellets without protectant no liposomes were found after processing. Adding KVA as a protectant before layering the liposomes onto the CELLETS® resulted in liposomes with z-avg. diameter of 171 nm and a PDI value of 0.26. Note that all liposomes before and after fluid bed processing, meet the quality criteria with a z-avg. diameter < 250 nm and acceptable PDI values of 0.2 – 0.3.

• Characterization of liposome-loaded pellets: Eyecon2 system measurements of processed liposome-loaded pellets indicated a compact structure and uniform size, demonstrating efficient processing (Figure 3). The increase in particle size (d50) compared to the original starting material is 96 – 122 μm for pellets after layering.

CONCLUSION

• This study demonstrates the effectiveness of fluid bed layering as a downstream technique for the development and manufacturing of liposomal formulations.
• The combination of FR-JET® technology and fluid bed processing achieved uniform particle sizes and compact product structures. Good redispersibility can be achieved when suitable protectants are added.
• This approach provides a unique strategy for solidifying liposomes using fluid bed processes to transfer liquid liposomal dispersions into dry, free-flowing granules or layered particles, keeping the integrity of the structures. In contrast to freeze-drying or spray-drying, fluid bed processes result in liposomes directly integrated in solid oral dosage forms.

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Source: Shuai Shi, Eleanor Lindenberg, Annette Grave, Liposomes Meet Fluidized Bed: From Lipid Vesicles to Solid Dosage for Liposomal Drug Delivery, Glatt, in collaboration with Leon Nanodrugs GmbH

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