title: Carrier particle design for stabilization and isolation of drug nanoparticles.
abstract: Nanoparticles of poorly water-soluble drugs were prepared in suspension via antisolvent precipitation in order to improve their dissolution behaviour. Insoluble, surface-functionalized, micron-range, clay carrier particles were employed for the dual purpose of stabilizing the nanoparticles in suspended state, and facilitating their unhindered isolation to solid state; often a challenging step in nanoparticle production. The carrier particles, which were functionalized with an optimal level of cationic polymer (protamine), attracted negatively-charged nanoparticles to their surface as a uniform and segregated nanoparticle layer, at drug loadings up to 9% w/w. By using carrier particles to stabilise the nanoparticles on their surface, the traditionally used solubilised nanosuspension stabilisers could be eliminated, thus avoiding time-consuming stabiliser screening tests. The carrier particle system facilitated stabilisation of nanoparticles in suspension, isolation of nanoparticles to the solid state via filtration, and preservation of fast nanoparticle-induced dissolution rates of the dried nanoparticle-carrier composites, indicating preservation of their high surface area during drying. The process was validated with two poorly water-soluble BCS Class II drugs, fenofibrate and mefenamic acid, both of which demonstrated negative surface charge in aqueous suspension.
authors.affiliation: Synthesis and Solid State Pharmaceutical Centre, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland. Electronic address: Teresa.Tierney@ul.ie.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tierney
authors.affiliation: Synthesis and Solid State Pharmaceutical Centre, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland. Electronic address: Katalin.Bodnar@ul.ie.
authors.forename: Katalin
authors.initials: K
authors.lastname: Bodnár
authors.affiliation: Synthesis and Solid State Pharmaceutical Centre, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland. Electronic address: Ake.Rasmuson@ul.ie.
authors.forename: Åke
authors.initials: Å
authors.lastname: Rasmuson
authors.affiliation: Synthesis and Solid State Pharmaceutical Centre, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland. Electronic address: Sarah.Hudson@ul.ie.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hudson
mesh_terms: D001546:Bentonite / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D011345:Fenofibrate / Q000737:chemistry; D008528:Mefenamic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D033362:Powder Diffraction; D011479:Protamines / Q000737:chemistry; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D011479:Protamines; D001546:Bentonite; D008528:Mefenamic Acid; D011345:Fenofibrate
keywords: Antisolvent precipitation; Bioavailability; Carrier particles; Dissolution rate; Drug nanoparticles; Filtration