Preparation of Co-amorphous Curcumin-tryptophan and Its Pharmacokinetic Study in Rats / 中国药房

ABSTRACT

OBJECTIVE：To prepare Co-amorphous curcumin （CUR）-tryptophan （TRY） （Co-amorphous CUR-TRY）， and to study its pharmacokinetic characteristics in rats. METHODS： Co-amorphous CUR-TRY was prepared by ball milling method. differential scanning calorimetry （DSC） and powder X-ray diffraction （XRD） were used to characterize Co-amorphous CUR-TRY. The in vitro dissolution rate （dissolution） of Co-amorphous CUR-TRY， CUR and CUR-TRY physical mixture were compared under sink condition and non-sink condition. 18 SD rats were selected and randomly divided into Co-amorphous CUR-TRY group （155.43 mg/kg）， CUR raw material group （100 mg/kg）， CUR-TRY physical mixture group （155.43 mg/kg）， with 6 rats in each group. They were given relevant medicine intragastrically once. Each blood samples 0.3 mL were collected from orbital venous plexus 0.167， 0.33， 0.5， 0.75， 1， 1.5， 2， 4， 6， 8， 10， 12， 24 h after medication. UPLC-MS/MS was used to determine plasma concentration of CUR in rats. The pharmacokinetic study was performed by using DAS 3.0 software. RESULTS： DSC and XRD showed that Co-amorphous CUR-TRY was successfully prepared. Under sink condition （120 min）， compared with CUR raw material [cumulative dissolution rate of CUR is （36.79±3.79）％] and CUR-TRY physical mixture [cumulative dissolution rate of CUR is （33.12±0.68）％]， cumulative dissolution rate of CUR in Co-amorphous CUR-TRY （90.37±2.52）％ was improved significantly （P＜0.01）. Under non-sink condition， compared with CUR raw material and CUR-TRY physical mixture， CUR of Co-amorphous CUR-TRY exhibited  dissolution and maintained supersaturation for a long time. Pharmacokinetic study showed that compared with CUR raw material group and CUR-TRY physical mixture group， cmax， AUC0-24 h and AUC0-∞ were increased significantly in Co-amorphous CUR-TRY group （P＜0.01）； Relative bioavailability of CUR  was improved by 2.14 and 1.86 fold （P＜0.01）. CONCLUSIONS：Prepared Co-amorphous CUR-TRY can effectively improve in vitro dissolution and in vivo bioavailability in rats of CUR.