3D-printing of lopinavir printlets by selective laser sintering and quantification of crystalline fraction by XRPD-chemometric models.

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 × 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.
(Copyright © 2020. Published by Elsevier B.V.)