Improving stability and oral bioavailability of hydroxycamptothecin via nanocrystals in microparticles (NCs/MPs) technology.

This study developed a nanocrystals-in-microparticles (NCs/MPs) technology for improving dissolution and oral absorption of poorly soluble drugs. Hydroxycamptothecin (HCPT) was selected as a model drug and prepared to be nanocrystals (HCPT-NCs) by acid-alkali based precipitation. The HCPT-NCs were rod like shape with the length of 250 nm and the width of 50 nm. Then, the chitosan and sodium alginate were selected as microparticles matrix to encapsulate the HCPT-NCs. The HCPT-NCs were entrapped in microparticles with a D value of 15 µm. The drug loading capacity of microparticles achieved more than 40% (w/w) by NCs/MPs technology. The powder X-ray diffraction showed the crystal structure of HCPT in microparticles was same as nanocrystals, indicating that the preparation of microparticles could not destroy the nanocrystals. The in vitro release demonstrated that microparticles could protect the NCs in gastric fluid and release NCs in intestinal fluid. Furthermore, the oral bioavailability of HCPT in NCs/MPs was improved by 18-fold compared to bulk HCPT and 2.1-fold compared to HCPT-NCs as tested by a rat model. Therefore, NCs/MPs technology is a promising and high effective approach to improve the oral bioavailability of poorly soluble drugs.