Preparation Of Curcumin Solid Dispersion Based On Green Technology And Its Evaluation In Vivo And In Vitro

Curcumin(CUR)has gained increasing interest worldwide due to multiple biological activities.However,CUR has low bioavailability because of its low aqueous solubility,intestinal metabolism and poor membrane permeability.In this study,two strategies were used to prepare CUR solid dispersion based on green technology to improve the bioavailability of CUR.First,the combination of piperine(PIP)and CUR was selected to prepare the non-carrier CUR-PIP co-amorphous solid dispersion.Second,chitosan oligosaccharide(COS)was selected as the green carrier,and CUR and COS were combined to prepare CUR-COS amorphous solid dispersionPreparation and evaluation of co-amorphous CUR-PIP:In present study,an excipient-free CUR solid dispersion co-formed with PIP,the absorption enhancer involving metabolism-permeability,was successfully prepared by quench cooling(co-amorphous CUR-PIP).The co-amorphous CUR-PIP exhibited superior performance in non-sink dissolution compared with crystalline and amorphous CUR,and showed physically stable at least 3 months,attributing to the strong molecular interactions between CUR and PIP as evaluated by FTIR spectra.Furthermore,the combination of PIP with CUR in the co-amorphous formulation could inhibit the glucuronidation of CUR,as exhibited in the in vitro assay of rat intestinal microsomes The co-amorphous CUR-PIP would also exhibit higher GI membrane permeability of CUR,as confirmed by Papp of CUR in Caco-2 model.After administration of co-amorphous CUR-PIP,the AUC of CUR significantly increased by 2.16-and 1.92-fold those in crystalline and amorphous CUR,respectively.This study demonstrates that the developed co-amorphous CUR-PIP can enhance the bioavailabilitry of CUR by increasing its dissolution,inhibiting metabolic processes,and facilitating membrane permeabilityPreparation and evaluation of CUR-COS ASD:Saccharides have been applied as a water-soluble matrix for homogeneously dispersing hydrophobic drugs without the need to use surfactants in amorphous solid dispersions(ASD).But concomitant permeability improvement of BCS Class IV drug by such matrixes have not been much appreciated up to now.Herein,an amorphous COS was used as matrix to prepare surfactant-free ASD of BCS class IV drug by ball-mill method,with CUR as a model drug.The DSC,XRPD,FTIR and physical stability experiments indicated that CUR was in an amorphous state with high physical stability and exhibited potential interactions with COS in the ASD.Non-sink dissolution in vitro studies showed the maximum dissolution concentration of all CUR-COS ASD reached ranging from 97.85 μg/mL to 101.21 μg/mL,far above those of pure CUR.The supersaturated concentration remained for at least 24 h under non-sink condition.Caco-2 cell model revealed that,compared to the pure CUR group,the apparent permeability coefficients were increased by 1.72-4.44-fold in all three CUR-COS ASD,which was mainly attributed to opening the tight junctions of Caco-2 cells by COS.Pharmacokinetic study showed that all CUR-COS ASD groups exhibited significant enhancements in AUC0-∞,with 1.55～3.01-times higher than that of pure CUR(p<0.01).Tmax of CUR was shortened after oral administration of all three ASD.Current study demonstrates the amorphous COS could be used as a promising matrix in ASD for enhancing the oral bioavailability of BCS class IV drug by improving dissolution behavior and membrane permeability.This study demonstrates that the developed co-amorphous CUR-PIP can improve the bioavailability of CUR by increasing its dissolution,inhibiting metabolic processes,and facilitating membrane permeability;the developed CUR-COS ASD can improve the bioavailability of CUR by increasing its dissolution and promoting membrane permeability Therefore,two kinds of CUR solid dispersion based on green technology were successfully prepared and the bioavailability of CUR was effectively improved.