3D-printing of lopinavir printlets by selective laser sintering and quantification of crystalline fraction by XRPD-chemometric models
3D-printing of lopinavir printlets by selective laser sintering and quantification of crystalline fraction by XRPD-chemometric models
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DOI：
10.1016/j.ijpharm.2020.120059
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发表时间：
2021-01-05
影响因子：
5.8
通讯作者：
Khan, Mansoor A.
中科院分区：
文献类型：
--
作者：
Hamed, Rania;Mohamed, Eman M.;Khan, Mansoor A.
本研究的目的是开发和表征无定形洛匹那韦（LPV）的印片，并通过X-射线粉末衍射（XRPD）-化学计量学模型来定量印片中LPV的结晶部分。通过选择性激光烧结（SLS）3D技术制造各种LPV浓度的无定形小印片（4.5mm直径X 3 mm高度）。的印刷品进行了表征的物理化学性质。XRPD数据结合化学计量学方法用于定量药物的结晶级分。印片中LPV含量为95.2- 100.9%，崩解时间< 2 min，溶出速度快（>90%的LPV在< 30 min内溶出）。小印片的孔隙率随着LPV百分比的增加而增加。印片的差示扫描量热法（DSC）和XRPD数据表明，大部分LPV以无定形形式存在。XRPD-化学计量学模型显示出良好的线性和低均方根误差、标准误差和偏差。模型验证表明，药物的结晶和无定形分数的实际值接近预测值。这些结果证明了通过SLS方法制造无定形印刷品的可行性，以及XRPD-化学计量学模型的应用，以量化3D制剂中的结晶药物的低分数，如果它们是由于工艺或环境相关变量而形成的。
The objectives of this study were to develop and characterize amorphous lopinavir (LPV) printlets and to the quantify crystalline fraction of LPV in the printlets by X-ray powder diffraction (XRPD)-chemometric models. Amorphous printlets (4.5 mm diameter x 3 mm height) of various LPV concentrations were fabricated by selective laser sintering (SLS) 3D technique. The printlets were characterized for physicochemical properties. The XRPD data in conjunction with chemometric method were used to quantify the crystalline fraction of the drug. The LPV content in the printlets was 95.2-100.9%, disintegration time was < 2 min, and dissolution was fast (>90% of LPV was dissolved in < 30 min). The porosity of the printlets increased with an increase in the LPV percentage. The differential scanning calorimetry (DSC) and XRPD data of the printlets demonstrated that the majority of LPV was present in amorphous form. The XRPD-chemometric models showed good linearity and low root mean squared error, standard error, and bias. Models validation showed that the actual values of crystalline and amorphous fractions of the drug were close to the predicted values. These results demonstrated the feasibility of fabricating amorphous printlets by SLS method, and the application of the XRPD-chemometric models to quantify low fractions of crystalline drug in the 3D formulations if they are formed due to process or environment related variables.