Development of a novel dry powder inhalation formulation for the delivery of rivastigmine hydrogen tartrate

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• 作者：Alice Simon^a ; ^b ; Maria Inê ; s Amaro^b ; Lucio Mendes Cabral^a ; Anne Marie Healy^b ; ^{healyam@tcd.ie" class="auth_mail" title="E-mail the corresponding author} ; Valeria Pereira de Sousa^a
• 关键词：API ; active pharmaceutical ingredients ; ATR-FTIR ; attenuated total reflection-FTIR spectroscopy ; DPI ; dry powder inhaler ; DSC ; differential scanning calorimetry ; DVS ; dynamic vapour sorption ; ED ; emitted recovered dose ; FPF ; fine particle fraction ; GSD ; geometric standard deviation ; HPLC ; high performance liquid chromatography ; Inu ; inulin ; LCF ; lactose carrier formulation ; Leu ; l-leucine ; MMAD ; mass median aerodynamic diameter ; NGI ; next generator impactor ; PXRD ; powder X-ray diffraction ; RH ; r
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 March 2016
• 年：2016
• 卷：501
• 期：1-2
• 页码：124-138
• 全文大小：2981 K

文摘

The purpose of this study was to prepare engineered particles of rivastigmine hydrogen tartrate (RHT) and to characterize the physicochemical and aerodynamic properties, in comparison to a lactose carrier formulation (LCF). Microparticles were prepared from ethanol/water solutions containing RHT with and without the incorporation of l-leucine (Leu), using a spray dryer. Dry powder inhaler formulations prepared were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, ATR-FTIR, differential scanning calorimetry, bulk and tapped density, dynamic vapour sorption and in vitro aerosol deposition behaviour using a next generation impactor. The smooth-surfaced spherical morphology of the spray dried microparticles was altered by adding Leu, resulting in particles becoming increasingly wrinkled with increasing Leu. Powders presented low densities. The glass transition temperature was sufficiently high (>90 °C) to suggest good stability at room temperature. As Leu content increased, spray dried powders presented lower residual solvent content, lower particle size, higher fine particle fraction (FPF < 5 μm), and lower mass median aerodynamic diameter (MMAD). The LCF showed a lower FPF and higher MMAD, relative to the spray dried formulations containing more than 10% Leu. Spray dried RHT powders presented better aerodynamic properties, constituting a potential drug delivery system for oral inhalation.