Mesophase and size manipulation of itraconazole liquid crystalline nanoparticles produced via quasi nanoemulsion precipitation.
The fabrication of drug nanoparticles (NPs) with process-mediated tunable properties and performances continues to grow rapidly during the last decades. This study investigates the synthesis and phase tuning of nanoparticulate itraconazole (ITR) mesophases using quasi nanoemulsion precipitation from acetone/water systems to seek out an alternative pathway to the nucleation-based NP formation. ITR liquid crystalline (LC) phases were formed and nematic-smectic mesomorphism was achieved via controlling solvent:antisolvent temperature difference (ΔTS:AS). The use of ΔTS:AS=49.5°C was associated with a nematic assembly, while intercalated smectic A layering was observed at ΔTS:AS=0°C, with both phases confined in the nanospheres at room temperature. The quasi emulsion system has not been investigated at the nanoscale to date and in contrary to the microscale, quasi nanoemulsion was observed over the solvent:antisolvent viscosity ratios of 1:7-1:1.4. Poly(acrylic acid) in the solvent phase exhibited a concentration dependent interaction when ITR formed NPs. This nanodroplet-based approach enabled the preparation of a stable ITR nanodispersion using Poloxamer 407 at 80°C, which was unachievable before using precipitation via nucleation. Findings of this work lay groundwork in terms of rationalised molecular assembly as a tool in designing pharmaceutical LC NPs with tailored properties.
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Naila A
NA
Mugheirbi
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland. Electronic address: lidia.tajber@tcd.ie.
Lidia
L
Tajber
D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry*; D011232:Chemical Precipitation; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D006358:Hot Temperature; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry*; D050866:Liquid Crystals; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity
D000935:Antifungal Agents; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D008823:Micelles; D012997:Solvents; D013501:Surface-Active Agents; D020442:Poloxamer; D017964:Itraconazole
Itraconazole; Liquid crystal; Nematic; Poloxamer 407; Quasi nanoemulsion; Smectic