Carrier particle design for stabilization and isolation of drug nanoparticles

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• 作者：Teresa Tierney ^{Teresa.Tierney@ul.ie} ; Katalin Bodná ; r ^{Katalin.Bodnar@ul.ie} ; Å ; ke Rasmuson ^{Ake.Rasmuson@ul.ie} ; Sarah Hudson ; ^{Sarah.Hudson@ul.ie}
• 关键词：Carrier particles ; Drug nanoparticles ; Bioavailability ; Antisolvent precipitation ; Filtration ; Dissolution rate
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：25 February 2017
• 年：2017
• 卷：518
• 期：1-2
• 页码：111-118
• 全文大小：1752 K
• 卷排序：518

文摘

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.