Development of stable amorphous solid dispersion and quantification of crystalline fraction of lopinavir by spectroscopic-chemometric methods

This study aimed to improve the dissolution of the poorly soluble drug lopinavir (LPV) by preparing amorphous solid dispersions (ASDs) using solvent evaporation method. The ASD formulations were prepared with ternary mixtures of LPV, Eudragit (R) E100, and microcrystalline cellulose (MCC) at various weight ratios. The ASDs were subjected to solid-state characterization and in vitro drug dissolution testing. Chemometric models based on near infrared spectroscopy (NIR) and NIR-hyperspectroscopy (NIR-H) data were developed using the partial least squares (PLS) regression and externally validated to estimate the percent of the crystalline LPV in the ASD. Initially, the solid-state characterization data of ASDs showed transformation of the drug from crystalline to amorphous. Negligible fraction of crystalline LPV was present in the ASD (3%). Compared to pure LPV, ASDs showed faster and higher drug dissolution (<2% vs. 60.3-73.5%) in the first 15 min of testing. The ASD was stable against crystallization during stability testing at 40 degrees C/75% for a month. In conclusion, the prepared ASD was stable against devitrification and enhance the dissolution of LPV.

Automated summary

This study aimed to improve the dissolution of the poorly soluble drug LPV by preparing amorphous solid dispersions (ASDs) using the solvent evaporation method. The ASDs showed a transformation of the drug from crystalline to amorphous, with only a negligible fraction of crystalline LPV present. Compared to pure LPV, the ASDs demonstrated faster and higher drug dissolution, and remained stable against crystallization during stability testing.