Lacidipine Amorphous Solid Dispersion Based on Hot Melt Extrusion: Good Miscibility, Enhanced Dissolution, and Favorable Stability
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The present study aimed to increase the in vitro dissolution rate of lacidipine, a poorly water-soluble drug, by formulating amorphous solid dispersions (ASDs) using hot-melt extrusion (HME). Differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, and Fourier transform infrared were used to characterize the optimal formulations and evaluate the physical stability for the stress test. Film-casting method and hot-stage microscopy were applied to study the miscibility of lacidipine and the drug carriers. In vitro dissolution tests were conducted as the final evaluation index. The optimal formulations were successfully obtained with Soluplus and PVP VA64 at a drug/carrier ratio of 1:10 (w/w), Fourier transform infrared studies revealed the hydrogen bonding between drug and polymers, and in vitro dissolution rates of the optimal formulations were extremely enhanced compared to bulk lacidipine and physical mixtures, similar with that of the commercial tablet. The ASD formulated with Soluplus showed better physical stability than that with PVP VA64. A strong hydrogen bonding and good drug-polymer miscibility were essential to hinder the recrystallization of lacidipine ASDs. In conclusion, the lacidipine ASD formulated with Soluplus showed a significant increase in in vitro dissolution rate and favorable physical stability in the stress test.
KEY WORDSlacidipine hot-melt extrusion dissolution amorphous solid dispersion physical stability
This work was financially supported by the National Nature Science Foundation of China (No. 81502993), by the Nature Science Foundation of Liaoning Province (No. 201700287), by the Basic Research Projects of Universities of Liaoning Provincial Department of Education (2017LQN02), and by the Career Development Program for Young Teachers in Shenyang Pharmaceutical University.
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