Co-precipitation of 10-hydroxycamptothecin and poly (l-lactic acid) by supercritical CO2 anti-solvent process using dichloromethane/ethanol co-solvent

In this study, 10-hydroxycamptothecin (HCPT) and poly (l-lactic acid) (PLLA) are co-precipitated by the supercritical anti-solvent (SAS) process using a mixture of dichloromethane (DCM)/ethanol (EtOH) as co-solvent, and supercritical carbon dioxide as the anti-solvent. The effect of five operating conditions on particle morphology, mass median diameter (Dp50) and HCPT loading is investigated using the single-factor method. The results indicate that HCPT loading can be greatly increased by using DCM/EtOH co-solvent, and the suitable operating conditions for the experimental system are determined. Under suitable conditions, the HCPT loading is 13.3% and Dp50 is 794.5 nm. The drug loaded microparticles are characterized in detail. The SEM images showed that most of the particles were spherical, and PLLA concentration has a major impact on the particle shape. Results of TEM, DSC and XRD indicate that the micronized HCPT is dispersed into the PLLA matrix. For low HCPT loading, most of HCPT existed in the drug loaded microparticles in an amorphous state, but for high HCPT loading, part of the encapsulated drug existed in crystalline form. FT-IR results show that SAS process does not change the chemical structure of HCPT. The result of in vitro drug release test indicated that the crystallinity of HCPT in microparticles affects the control release performance, and the good encapsulated microparticles with higher HCPT loading and higher crystallinity are better.

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► HCPT and PLLA are co-precipitated by supercritical anti-solvent process using dichloromethane/ethanol co-solvent.
► The co-solvent has great effect on HCPT loading.
► HCPT is dispersed into the PLLA matrix.
► Drug existing in a crystalline form increases with an increase in HCPT loading.
► Good encapsulated microparticles with higher HCPT loading and higher crystallinity are better for control release of HCPT.