کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5821415 | 1557434 | 2011 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Pharmaceutical NanotechnologyEvaluation of a crystalline nanosuspension: Polymorphism, process induced transformation and in vivo studies Pharmaceutical NanotechnologyEvaluation of a crystalline nanosuspension: Polymorphism, process induced transformation and in vivo studies](/preview/png/5821415.png)
The aim of this work was to evaluate a crystalline nanosuspension of an investigational anticancer compound, SN 30191. Solid forms of SN 30191 were prepared and characterized by thermal analysis, infrared spectroscopy, 13C CP/MAS SSNMR spectroscopy, SEM and powder XRD. Wet milling was performed using a high pressure homogenizer and process induced transformations were studied as a function of time and pressure using infrared spectroscopy. Dose-toxicity and pharmacokinetics (PK) of the nanocrystal formulation were evaluated in mice after intravenous administration. SN 30191 was found to exist in two polymorphic forms (I and II) and a hydrate with an equilibrium solubility < 0.1 μg/ml (pH 1.3-11.0, 37 °C). Wet milling resulted in solid state transformation as a function of pressure. Form II was found to transform into form I at intermediate pressures. A further increase in pressure resulted in formation of a hydrate. The final nanosuspension consisted of SN 30191 as a hydrate. The dose-toxicity studies revealed higher tolerance (â¼4 times) for the nanosuspension (10 mg/kg) when compared with a solution formulation (2.5 mg/kg). Compared with solution formulation, the nanosuspension allowed the delivery of a higher dose and rendered possible the performance of PK and tissue distribution studies in animals.
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Journal: International Journal of Pharmaceutics - Volume 408, Issues 1â2, 15 April 2011, Pages 138-151