Evaluation of microstructure, dissolution rate, and oral bioavailability of paclitaxel poloxamer 188 solid dispersion.

Abstract

Poor solubility is a major challenge for enhancing the oral bioavailability and clinical application of many drugs, including the broad-spectrum chemotherapy drug paclitaxel (PTX). A practical approach to improving the solubility of insoluble drugs is through the use of solid dispersion (SD).This study aimed to investigate the potential of the triblock copolymer, poloxamer 188 (P188), as a carrier for preparing solid dispersion of paclitaxel using spray drying technology. We systematically studied its microstructure, dissolution behavior in vitro, and pharmacokinetics. Our findings demonstrate that PTX exists in an amorphous state in copolymer composed of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) P188, with stronger miscibility with hydrophobic PPO segments. All three in vitro dissolution models revealed that the release rate of drugs in SD was significantly higher compared to that of physical mixtures (PM) as well as raw drugs. Furthermore, our pharmacokinetic results showed that the area under the curve(AUC) of PTX in SD was 6 times higher than that of active pharmaceutical ingredient(API), 4.5 times higher than PM, and the highest blood drug concentration (Cmax) reached 357.51 ± 125.54 (ng/mL), approximately 20 times higher than API.Overall, our findings demonstrate that the dissolution rate of amorphous PTX in SD significantly improves, effectively enhancing the oral bioavailability of PTX.