Abstract
In this thesis, a freeze-dried donepezil HCl liposomal formulation was developed as a reconstitutable product designed for brain-targeted delivery via intranasal administration. The liposomal composition in this formulation was based on the previous work and comprised: soy phosphatidylcholine (SPC), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and dimethyldioctadecylammonium bromide (DDAB). A new organic solvent-free method (OSF) for liposome preparation was developed, which does not require organic solvent, is time efficient and is as effective as the thin film hydration method (TFH) in producing liposomes with optimum properties. As a freeze-dried product, the inclusion of 15% or 18% trehalose as a lyoprotectant stabilised vesicles against aggregation, fusion, and drug leakage after reconstitution, producing liposomes with size ~100nm, homogenous dispersion with polydispersity index (PdI) of < 0.25, encapsulation efficiency (EE%) of > 70%, controlled release pattern and gave rise to physically stable freeze-dried cakes with high glass transition (Tg > 70°C) and low water content (< 3%). The formulation offered the additional advantage of high drug content, matching the dose in currently marketed oral preparations. Freeze-dried donepezil HCl liposomal products with different trehalose concentrations and pH were analysed for their storage stability at 20°C and 40°C. It was found that donepezil HCl liposomes prepared at pH 7.40 and containing 18% trehalose showed an acceptable stability profile at 20°C, preserving the product properties within the desired range for up to 24 weeks.A similar liposomal composition was used to manufacture freeze-dried ovalbumin-loaded liposomes as a model antigen intended for nasal vaccination using the OSF method. The optimised liposomal formulation contained 0.1% (w/v) ovalbumin, 3.8% (w/v) lipid, including DDAB at 0.6% (w/v) and 18% trehalose.
Collectively, the study showed the potential of the liposomal system as a carrier for nasal application. Owing to its facile and efficient manufacturing method, this liposomal product could be cost-effective, reducing the demand for a “cold chain” and prolonging product shelf-life.
Thesis is embargoed until 31 July 2026.
| Date of Award | Jul 2023 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Vicky Kett (Supervisor) & Mark Mooney (Supervisor) |