Investigations into manufacturing processes for a liposomal parenteral nanoformulation to solubilize poorly soluble drug substance

Abstract

Background/Objectives: Some pharmaceutical products have poor water solubility thus parenteral formulation strategy is to use liposomal nanomedicine for solubilization. This avoids the use of larger quantities of co-solvents and/or polyoxyethylene based surfactants which are associated with severe side-effects. To reduce such limitations, a poorly soluble drug substance was nanoformulated by packaging into liposomes made from natural phospholipids. Methods/Statistical analysis: The top-down and bottom-up approach of nanoformulation were investigated with an aim to get the desired properties. Particle size, polydispersity index and zeta potential were determined by photon correlation spectroscopy using a zeta sizer. The effect of process parameters such as homogenization pressure, number of homogenization cycles, lipid concentration and the effect of addition of buffer components were equally investigated. Findings: The mean particle size for the bottom-up process was 46.0 nm but the encapsulation efficiency was below 30% indicating most of the drug substance is washed away. The top-down approach gave mean particle sizes of about 80.0 nm and the encapsulation efficiency was almost 100% after performing thermodynamic stability. This was evident as crystals were not observed from the polarized light microscope. Increase in homogenization pressure and number of cycles significantly (p≤0.05) reduced the particle sizes and polydispersity index (PDI). Liposomes with a narrow distribution were obtained when higher lipid concentrated liposome dispersion was progressively diluted to lower concentration followed by addition of buffer components. Improvements/ Applications: Liposomal formulations composed of natural phospholipids proved to be an interesting tool for solubilization of poorly soluble compounds for parenteral administration. Key words: Nanomedicine, liposomes, parenteral, phospholipids, lyophilization 1