Preparation of Lapatinib Ditosylate Solid Dispersions by Freeze-drying Technology and Its Pharmacokinetic Evaluation in Rats

OBJECTIVE To improve lapatinib ditosylate's bioavailability by preparation of its solid dispersion with freeze-drying mothod. METHODS The solid dispersion was prepared by freeze-drying method using PVPS630 and soluplus^® as carriers, respectively. The solid dispersion was characterized using SEM, DSC and XRPD. The apparent solubility, dissolution and pharmacokinetics in rats were determined to evaluate the solubilization effect and the improvement of bioavailability of the solid dispersion. RESULTS With the same drug loading ratio, the dissolution and solubility of the PVPS630 group were both better than those of the soluplus^® group. DSC, XRPD, SEM characterization results also exhibited that raw material was amorphous in all proportion groups when the carrier was PVPS630. While the raw material exhibited amorphous characteristic only when the drug loading ratio was 1:3 (lapatinib ditosylate-soluplus^®) in the soluplus^® groups. The results of rat pharmacokinetic showed that the AUC of solid dispersion (lapatinib ditosylate-PVPS630 1:3) was 23.64% higher than that of reference drug. CONCLUSION The compatibility of PVPS630 with lapatinib ditosylate is better than soluplus^®; and the solid dispersion technology is useful to improve the bioavailability of lapatinib ditosylate.