Hydrochloride salt co-crystals: preparation, characterization and physicochemical studies
Hydrochloride salt co-crystals: preparation, characterization and physicochemical studies
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盐酸盐共晶：制备、表征和理化研究
DOI：
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发表时间：
2013
期刊：
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通讯作者：
Shailesh A Shah
中科院分区：
文献类型：
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作者：
V. Parmar;Shailesh A Shah
提出了用共结晶法对盐酸盐的物理化学性质进行改性。目的：研究不同共晶型共结晶对盐酸氟西汀(FH)理化性质的影响。采用慢蒸发法筛选出FH与一系列羧酸异构体共结晶。测定了结晶相的显微照片和熔点。用红外光谱、差示扫描量热仪和X射线衍射仪对共晶进行了表征。测定了共晶体在水和缓冲溶液中的溶解度。对共晶体的粉末和本征溶出度进行了评估。药物和异构体的物理混合物用于在表征和物理化学性质评价阶段进行比较。四种FH的共晶，即。通过筛选实验得到了盐酸氟西汀-马来酸(FH-MA)、盐酸氟西汀-戊二酸(FH-GA)、盐酸氟西汀-L-酒石酸(FH-LTA)和盐酸氟西汀-DL-酒石酸(FH-DLTA)。物理表征表明，它们具有独特的晶体形态、热性能、光谱性能和X射线衍射性能。溶出度和溶出度研究表明，盐酸氟西汀-马来酸共晶在蒸馏水、pH 4.6、7.0缓冲溶液中的溶解度和在蒸馏水中的溶出度均高于纯药物。离子原料药可以采用共晶形成的方法来调整其物理性质。
Co-crystallization approach for modification of physicochemical properties of hydrochloride salt is presented. The objective of this investigation was to study the effect of co-crystallization with different co-crystal formers on physicochemical properties of fluoxetine hydrochloride (FH). FH was screened for co-crystallization with a series of carboxylic acid co-formers by slow evaporation method. Photomicrographs and melting points of crystalline phases were determined. The co-crystals were characterized by FTIR, DSC and PXRD methods. Solubility of co-crystals was determined in water and buffer solutions. Powder and intrinsic dissolution profiles were assessed for co-crystals. Physical mixtures of drug and co-formers were used for comparisons at characterizations and physicochemical properties evaluation stages. Four co-crystals of FH viz. Fluoxetine hydrochloride-maleic acid (FH-MA), Fluoxetine hydrochloride-glutaric acid (FH-GA), Fluoxetine hydrochloride-L-tartaric acid (FH-LTA) and Fluoxetine hydrochloride-DL-tartaric acid (FH-DLTA) were obtained from screening experiments. Physical characterization showed that they have unique crystal morphology, thermal, spectroscopic and X-ray diffraction properties. Solubility and dissolution studies showed that Fluoxetine hydrochloride-maleic acid co-crystal possess high aqueous solubility in distilled water, pH 4.6, 7.0 buffer solutions and dissolution rate in distilled water than that of pure drug. Co-crystal formation approach can be used for ionic API to tailor its physical properties.