Odetade David F, Vladisavljevic Goran T
Department of Chemical Engineering, Loughborough University, Epinal Way, Loughborough, Leicestershire LE11 3TU, UK.
Micromachines (Basel). 2016 Dec 18;7(12):236. doi: 10.3390/mi7120236.
Hydrocortisone (HC) nanocrystals intended for parenteral administration of HC were produced by anti-solvent crystallisation within coaxial assemblies of pulled borosilicate glass capillaries using either co-current flow of aqueous and organic phases or counter-current flow focusing. The organic phase was composed of 7 mg/mL of HC in a 60:40 (/) mixture of ethanol and water and the anti-solvent was milli-Q water. The microfluidic mixers were fabricated with an orifice diameter of the inner capillary ranging from 50 µm to 400 µm and operated at the aqueous to organic phase flow rate ratio ranging from 5 to 25. The size of the nanocrystals decreased with increasing aqueous to organic flow rate ratio. The counter-current flow microfluidic mixers provided smaller nanocrystals than the co-current flow devices under the same conditions and for the same geometry, due to smaller diameter of the organic phase stream in the mixing zone. The Z-average particle size of the drug nanocrystals increased from 210⁻280 nm to 320⁻400 nm after coating the nanocrystals with 0.2 wt % aqueous solution of hydroxypropyl methylcellulose (HPMC) in a stirred vial. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analyses carried out on the dried nanocrystals stabilized with HPMC, polyvinyl pyrrolidone (PVP), and sodium lauryl sulfate (SLS) were investigated and reported. The degree of crystallinity for the processed sample was lowest for the sample stabilised with HPMC and the highest for the raw HC powder.
用于氢化可的松肠胃外给药的氢化可的松(HC)纳米晶体,是通过在拉制的硼硅酸盐玻璃毛细管的同轴组件内进行抗溶剂结晶来制备的,使用水相和有机相并流或逆流聚焦。有机相由7 mg/mL的HC溶解在乙醇和水的60:40(/)混合物中组成,抗溶剂为超纯水。微流混合器的内毛细管孔直径为50 µm至400 µm,水相和有机相流速比为5至25时运行。纳米晶体的尺寸随着水相和有机相流速比的增加而减小。在相同条件和相同几何形状下,逆流微流混合器比并流装置产生的纳米晶体更小,这是因为混合区中有机相流的直径更小。在用0.2 wt%羟丙基甲基纤维素(HPMC)水溶液在搅拌瓶中包覆纳米晶体后,药物纳米晶体的Z平均粒径从210⁻280 nm增加到320⁻400 nm。对用HPMC、聚乙烯吡咯烷酮(PVP)和十二烷基硫酸钠(SLS)稳定的干燥纳米晶体进行了差示扫描量热法(DSC)和X射线粉末衍射(XRPD)分析并进行了报道。用HPMC稳定的样品的加工样品结晶度最低,而原始HC粉末的结晶度最高。
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