Development and activity testing of spray dried Phosphorylated Hexaacyl Disaccharide for nasal administration
Jasmine Ahad1, Jack Sorrell1, Laura Mason1, Kristine Storey2 & Joe Ninosky2
1Upperton Pharma Solutions, Albert Einstein Centre, Nottingham Science and Technology Park, Nottingham, NG7 2TN, United Kingdom
2Revelation Biosciences Inc., 11011 Torreyana Road, Suite 102, San Diego, CA 92121, United States
Summary
Derived from the lipopolysaccharide fraction of the cell walls within Gram negative bacteria, Phosphorylated Hexaacyl Disaccharide (PHAD) activates Toll-like receptor 4 (TLR4) leading to the production of cytokines, activation of CD4+ and CD8+ T cells, and the activation of the adaptive immune response. This has potential applications for the prevention and/or treatment of respiratory viral infection and allergies, and so a product for nasal administration is targeted. However, PHAD is poorly soluble in aqueous formulations, and may incur stability issues due to hydrolysis. Thus, investigations were conducted to produce a dry powder PHAD formulation (2:49:49 %w/w/w PHAD:Hydroxypropyl-β-Cyclodextrin:Trehalose) by spray drying to increase long-term stability and improve aqueous solubility. The optimum feed solution preparation process to generate micellar PHAD for spray drying has been investigated. Reconstitution of the resultant powder formulations at 0.6 mg/mL PHAD in water found that decreasing the concentration of PHAD within the spray drying feed solution resulted in improved reconstitution of the spray dried PHAD formulation, with faster dissolution and reduced solution turbidity observed. In addition, micelle diameter distributions by dynamic light scattering (DLS) showed a trend towards uniformity as the feed solution concentration was reduced. As a result, it was identified that a concentration of 0.5 mg/mL PHAD in the initial spray drying feed solution balanced spray drying efficiency and quality of micelles when reconstituted. Spray dried PHAD also maintained similar biological activity to unprocessed PHAD in solution. The spray dried PHAD will be further investigated as a stable form of PHAD that can be administered intranasally, either as a reconstituted solution or as a powder.
Key Message
Spray dried PHAD formulation has been developed for administration as a micellar nasal spray to treat viral respiratory infections and allergies. Investigations found that PHAD concentration within spray drying feed solutions influenced the reconstitution properties of the resultant powder formulations, with reconstitution time, solution turbidity and micelle uniformity affected.