title: Drug solubilisation in lipid nanoparticles containing high melting point triglycerides.
abstract: The effect of lipid (either the triglyceride trilaurin or tripalmitin, melting points of 43 and 64 °C, respectively) on the properties of lipid nanoparticles (LN) stabilised by the surfactant, polyoxyethylene-10-oleyl ether (C18:1E10) at a temperature of 22 °C, has been determined. LN were prepared by heating lipid, surfactant and water to 70 °C and cooling to ambient temperature with constant stirring. While lipid type influenced LN formation in that trilaurin-containing LN formed over the greatest range of compositions, phase inversion studies suggested that both lipids formed a core within the LN while light scattering studies indicated that the size of both types of LN varied with lipid concentration: in an approximately linear fashion for clear or opalescent LN and exponentially for cloudy LN. Additionally, both types of preformed LN exhibited an increase in solubilisation capacity of the hydrophobic drug, testosterone propionate compared to C18:1E10 micelles, although the trilaurin-containing LN exhibited the greatest increase. Differential scanning calorimetry studies demonstrated that trilaurin formed a 'fluid-like' core and therefore liquefied-lipid nanoparticles, which allowed dissolution of testosterone propionate in the lipid core. In contrast, tripalmitin was present in a 'solid-like' state forming solid lipid nanoparticles which did not allow testosterone propionate dissolution in the core.
authors.affiliation: Pharmaceutical Biophysics Group, Institute of Pharmaceutical Science, King's College London, London, UK; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Prawarisa
authors.initials: P
authors.lastname: Wasutrasawat
authors.forename: Hisham
authors.initials: H
authors.lastname: Al-Obaidi
authors.forename: Simon
authors.initials: S
authors.lastname: Gaisford
authors.forename: M Jayne
authors.initials: MJ
authors.lastname: Lawrence
authors.forename: Warangkana
authors.initials: W
authors.lastname: Warisnoicharoen
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D008055:Lipids / Q000737:chemistry; D008823:Micelles; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013696:Temperature; D043343:Testosterone Propionate / Q000008:administration & dosage / Q000737:chemistry*; D044366:Transition Temperature; D014280:Triglycerides / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D008055:Lipids; D008823:Micelles; D013501:Surface-Active Agents; D014280:Triglycerides; C478746:polyoxyethylene-10-oleyl ether; D014867:Water; D011092:Polyethylene Glycols; C004565:trilaurin; C005859:tripalmitin; D043343:Testosterone Propionate
keywords: C(18:1)E(10); Nanoparticles; Polyoxyethylene-10-oleyl ether; Solubilisation; Triglycerides; testosterone propionate