A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein
|
摘要
Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.
Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.
Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.
引文
[1]Takagi T,Ramachandran C,Bermejo M,et al.A provisional biopharmaceutical classification of the top 200 oral drug products in the United States,Great Britain,Spain,and Japan.Mol Pharm 2006;3(6):631-43.
[2]Ashour EA,Majumdar S,Alsheteli A,et al.Hot melt extrusion as an approach to improve solubility,permeability and oral absorption of a psychoactive natural product,piperine.JPharm Pharmacol 2016;68(8):989-98.
[3]Hao Y,Wang L,Li J,et al.Enhancement of solubility,transport across Madin-Darby Canine Kidney monolayers and oral absorption of Pranlukast through preparation of a Pranlukast-phospholipid complex.J Biomed Nanotechnol2015;11(3):469-77.
[4]Kim MS,Kim JS,Cho WK,Hwang SJ.Enhanced solubility and oral absorption of sirolimus using D-alpha-tocopheryl polyethylene glycol succinate micelles.Artif Cells Nanomed Biotechnol 2013;41(2):85-91.
[5]Qiao N,Li M,Schlindwein W,et al.Pharmaceutical cocrystals:an overview.Int J Pharm 2011;419(1-2):1-11.
[6]Thakuria R,Delori A,Jones W,et al.Pharmaceutical cocrystals and poorly soluble drugs.Int J Pharm2013;453(1):101-25.
[7]Rahman Z,Agarabi C,Zidan AS,Khan SR,Khan MA.Physico-mechanical and stability evaluation of carbamazepine cocrystal with nicotinamide.AAPSPharmSciTech 2011;12(2):693-704.
[8]Tomaszewska I,Karki S,Shur J,Price R,Fotaki N.Pharmaceutical characterisation and evaluation of cocrystals:importance of in vitro dissolution conditions and type of coformer.Int J Pharm 2013;453(2):380-8.
[9]Hong C,Xie Y,Yao Y,et al.A novel strategy for pharmaceutical cocrystal generation without knowledge of stoichiometric ratio:myricetin cocrystals and a ternary phase diagram.Pharm Res 2015;32(1):47-60.
[10]Huang Y,Zhang B,Gao Y,Zhang J,Shi L.Baicalein-nicotinamide cocrystal with enhanced solubility,dissolution,and oral bioavailability.J Pharm Sci2014;103(8):2330-7.
[11]McNamara DP,Childs SL,Giordano J,et al.Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API.Pharm Res 2006;23(8):1888-97.
[12]Müller RH,Keck CM.Twenty years of drug nanocrystals:Where are we,and where do we go?Eur J Pharm Biopharm2012;80(1):1-3.
[13]Pi J,Liu Z,Wang H,et al.Ursolic acid nanocrystals for dissolution rate and bioavailability enhancement:influence of different particle size.Curr Drug Deliv 2016;13(8):1358-66.
[14]Zuo B,Sun Y,Li H,et al.Preparation and in vitro/in vivo evaluation of fenofibrate nanocrystals.Int J Pharm2013;455(1-2):267-75.
[15]Zhang J,Lv H,Jiang K,Gao Y.Enhanced bioavailability after oral and pulmonary administration of baicalein nanocrystal.Int J Pharm 2011;420(1):180-8.
[16]Hao L,Wang X,Zhang D,et al.Studies on the preparation,characterization and pharmacokinetics of Amoitone Bnanocrystals.Int J Pharm 2012;433(1-2):157-64.
[17]Kesisoglou F,Panmai S,Wu Y.Nanosizing-oral formulation development and biopharmaceutical evaluation.Adv Drug Deliv Rev 2007;59(7):631-44.
[18]Junghanns JU,Muller RH.Nanocrystal technology,drug delivery and clinical applications.Int J Nanomedicine2008;3(3):295-309.
[19]De Smet L,Saerens L,De Beer T,et al.Formulation of itraconazole nanococrystals and evaluation of their bioavailability in dogs.Eur J Pharm Biopharm2014;87(1):107-13.
[20]Karashima M,Kimoto K,Yamamoto K,Kojima T,Ikeda Y.Anovel solubilization technique for poorly soluble drugs through the integration of nanocrystal and cocrystal technologies.Eur J Pharm Biopharm 2016;107:142-50.
[21]Liu M,Hong C,Li G,Ma P,Xie Y.The generation of myricetin-nicotinamide nanococrystals by top down and bottom up technologies.Nanotechnology 2016;27(39):395601.
[22]Huang Y,Li JM,Lai ZH,et al.Phenazopyridine-phthalimide nano-cocrystal:Release rate and oral bioavailability enhancement.Eur J Pharm Sci 2017;109:581-6.
[23]Miocinovic R,McCabe NP,Keck RW,et al.In vivo and in vitro effect of baicalein on human prostate cancer cells.Int JOncol 2005;26(1):241-6.
[24]Fan GW,Zhang Y,Jiang X,et al.Anti-inflammatory activity of baicalein in LPS-stimulated RAW264.7 macrophages via estrogen receptor and NF-kappaB-dependent pathways.Inflammation 2013;36(6):1584-91.
[25]Huang Y,Tsang SY,Yao X,Chen ZY.Biological properties of baicalein in cardiovascular system.Curr Drug Targets Cardiovasc Haematol Disord 2005;5(2):177-84.
[26]Sowa M,Slepokura K,Matczak-Jon E.A 1:1 cocrystal of baicalein with nicotinamide.Acta Crystallogr C 2012;68(Pt7):262-5.
[27]Zeng L,Wang M,Yuan Y,et al.Simultaneous multi-component quantitation of Chinese herbal injection Yin-zhi-huang in rat plasma by using a single-tube extraction procedure for mass spectrometry-based pharmacokinetic measurement.J Chromatogr B Analyt Technol Biomed Life Sci 2014;967:245-54.
[28]Xie Y,Hao H,Kang A,et al.Integral pharmacokinetics of multiple lignan components in normal,CCl4-induced hepatic injury and hepatoprotective agents pretreated rats and correlations with hepatic injury biomarkers.JEthnopharmacol 2010;131(2):290-9.
[29]Karki S,Friscic T,Jones W,Motherwell WD.Screening for pharmaceutical cocrystal hydrates via neat and liquid-assisted grinding.Mol Pharm 2007;4(3):347-54.
[30]Dhumal RS,Kelly AL,York P,Coates PD,Paradkar A.Cocrystalization and simultaneous agglomeration using hot melt extrusion.Pharm Res 2010;27(12):2725-33.
[31]Brough C,Williams RO 3rd.Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery.Int J Pharm 2013;453(1):157-66.
[32]Hasa D,Voinovich D,Perissutti B,et al.Reduction of melting temperature and enthalpy of drug crystals:theoretical aspects.Eur J Pharm Sci 2013;50(1):17-28.
[33]Kerr HE,Softley LK,Suresh K,Hodgkinson P,Evans IR.Structure and physicochemical characterization of a naproxen-picolinamide cocrystal.Acta Crystallogr C Struct Chem 2017;73(Pt 3):168-75.
[34]Hecq J,Deleers M,Fanara D,et al.Preparation and in vitro/in vivo evaluation of nano-sized crystals for dissolution rate enhancement of ucb-35440-3,a highly dosed poorly water-soluble weak base.Eur J Pharm Biopharm2006;64(3):360-8.
[35]Gao L,Liu G,Ma J,et al.Drug nanocrystals:In vivo performances.J Control Release 2012;160(3):418-30.
[36]Shegokar R,Muller RH.Nanocrystals:industrially feasible multifunctional formulation technology for poorly soluble actives.Int J Pharm 2010;399(1-2):129-39.
[37]Tu L,Yi Y,Wu W,et al.Effects of particle size on the pharmacokinetics of puerarin nanocrystals and microcrystals after oral administration to rat.Int J Pharm2013;458(1):135-40.
[38]Akao T,Sato K,Hanada M.Hepatic contribution to a marked increase in the plasma concentration of baicalin after oral administration of its aglycone,baicalein,in multidrug resistance-associated protein 2-deficient rat.Biol Pharm Bull2009;32(12):2079-82.
[39]Zhang L,Lin G,Chang Q,Zuo Z.Role of intestinal first-pass metabolism of baicalein in its absorption process.Pharm Res2005;22(7):1050-8.
[40]Kang MJ,Ko GS,Oh DG,et al.Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin.Arch Pharm Res 2014;37(3):371-8.
[41]Wang J,Pang Q,Cen W,Zhu P,Xu Y.Simultaneous determination of ten active constituents of Yankening Capsule in rat plasma by ultra high performance liquid chromatography with tandem mass spectrometry.JChromatogr B Analyt Technol Biomed Life Sci2015;978-979:43-53.
[42]Qian P,Zhang YB,Yang YF,Xu W,Yang XW.Pharmacokinetics studies of 12 alkaloids in rat plasma after oral administration of Zuojin and Fan-Zuojin formulas.Molecules 2017;22(2):214.
[43]Alam MA,Al-Jenoobi FI,Al-mohizea AM.Commercially bioavailable proprietary technologies and their marketed products.Drug Discov Today 2013;18(19-20):936-49.
[2]Ashour EA,Majumdar S,Alsheteli A,et al.Hot melt extrusion as an approach to improve solubility,permeability and oral absorption of a psychoactive natural product,piperine.JPharm Pharmacol 2016;68(8):989-98.
[3]Hao Y,Wang L,Li J,et al.Enhancement of solubility,transport across Madin-Darby Canine Kidney monolayers and oral absorption of Pranlukast through preparation of a Pranlukast-phospholipid complex.J Biomed Nanotechnol2015;11(3):469-77.
[4]Kim MS,Kim JS,Cho WK,Hwang SJ.Enhanced solubility and oral absorption of sirolimus using D-alpha-tocopheryl polyethylene glycol succinate micelles.Artif Cells Nanomed Biotechnol 2013;41(2):85-91.
[5]Qiao N,Li M,Schlindwein W,et al.Pharmaceutical cocrystals:an overview.Int J Pharm 2011;419(1-2):1-11.
[6]Thakuria R,Delori A,Jones W,et al.Pharmaceutical cocrystals and poorly soluble drugs.Int J Pharm2013;453(1):101-25.
[7]Rahman Z,Agarabi C,Zidan AS,Khan SR,Khan MA.Physico-mechanical and stability evaluation of carbamazepine cocrystal with nicotinamide.AAPSPharmSciTech 2011;12(2):693-704.
[8]Tomaszewska I,Karki S,Shur J,Price R,Fotaki N.Pharmaceutical characterisation and evaluation of cocrystals:importance of in vitro dissolution conditions and type of coformer.Int J Pharm 2013;453(2):380-8.
[9]Hong C,Xie Y,Yao Y,et al.A novel strategy for pharmaceutical cocrystal generation without knowledge of stoichiometric ratio:myricetin cocrystals and a ternary phase diagram.Pharm Res 2015;32(1):47-60.
[10]Huang Y,Zhang B,Gao Y,Zhang J,Shi L.Baicalein-nicotinamide cocrystal with enhanced solubility,dissolution,and oral bioavailability.J Pharm Sci2014;103(8):2330-7.
[11]McNamara DP,Childs SL,Giordano J,et al.Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API.Pharm Res 2006;23(8):1888-97.
[12]Müller RH,Keck CM.Twenty years of drug nanocrystals:Where are we,and where do we go?Eur J Pharm Biopharm2012;80(1):1-3.
[13]Pi J,Liu Z,Wang H,et al.Ursolic acid nanocrystals for dissolution rate and bioavailability enhancement:influence of different particle size.Curr Drug Deliv 2016;13(8):1358-66.
[14]Zuo B,Sun Y,Li H,et al.Preparation and in vitro/in vivo evaluation of fenofibrate nanocrystals.Int J Pharm2013;455(1-2):267-75.
[15]Zhang J,Lv H,Jiang K,Gao Y.Enhanced bioavailability after oral and pulmonary administration of baicalein nanocrystal.Int J Pharm 2011;420(1):180-8.
[16]Hao L,Wang X,Zhang D,et al.Studies on the preparation,characterization and pharmacokinetics of Amoitone Bnanocrystals.Int J Pharm 2012;433(1-2):157-64.
[17]Kesisoglou F,Panmai S,Wu Y.Nanosizing-oral formulation development and biopharmaceutical evaluation.Adv Drug Deliv Rev 2007;59(7):631-44.
[18]Junghanns JU,Muller RH.Nanocrystal technology,drug delivery and clinical applications.Int J Nanomedicine2008;3(3):295-309.
[19]De Smet L,Saerens L,De Beer T,et al.Formulation of itraconazole nanococrystals and evaluation of their bioavailability in dogs.Eur J Pharm Biopharm2014;87(1):107-13.
[20]Karashima M,Kimoto K,Yamamoto K,Kojima T,Ikeda Y.Anovel solubilization technique for poorly soluble drugs through the integration of nanocrystal and cocrystal technologies.Eur J Pharm Biopharm 2016;107:142-50.
[21]Liu M,Hong C,Li G,Ma P,Xie Y.The generation of myricetin-nicotinamide nanococrystals by top down and bottom up technologies.Nanotechnology 2016;27(39):395601.
[22]Huang Y,Li JM,Lai ZH,et al.Phenazopyridine-phthalimide nano-cocrystal:Release rate and oral bioavailability enhancement.Eur J Pharm Sci 2017;109:581-6.
[23]Miocinovic R,McCabe NP,Keck RW,et al.In vivo and in vitro effect of baicalein on human prostate cancer cells.Int JOncol 2005;26(1):241-6.
[24]Fan GW,Zhang Y,Jiang X,et al.Anti-inflammatory activity of baicalein in LPS-stimulated RAW264.7 macrophages via estrogen receptor and NF-kappaB-dependent pathways.Inflammation 2013;36(6):1584-91.
[25]Huang Y,Tsang SY,Yao X,Chen ZY.Biological properties of baicalein in cardiovascular system.Curr Drug Targets Cardiovasc Haematol Disord 2005;5(2):177-84.
[26]Sowa M,Slepokura K,Matczak-Jon E.A 1:1 cocrystal of baicalein with nicotinamide.Acta Crystallogr C 2012;68(Pt7):262-5.
[27]Zeng L,Wang M,Yuan Y,et al.Simultaneous multi-component quantitation of Chinese herbal injection Yin-zhi-huang in rat plasma by using a single-tube extraction procedure for mass spectrometry-based pharmacokinetic measurement.J Chromatogr B Analyt Technol Biomed Life Sci 2014;967:245-54.
[28]Xie Y,Hao H,Kang A,et al.Integral pharmacokinetics of multiple lignan components in normal,CCl4-induced hepatic injury and hepatoprotective agents pretreated rats and correlations with hepatic injury biomarkers.JEthnopharmacol 2010;131(2):290-9.
[29]Karki S,Friscic T,Jones W,Motherwell WD.Screening for pharmaceutical cocrystal hydrates via neat and liquid-assisted grinding.Mol Pharm 2007;4(3):347-54.
[30]Dhumal RS,Kelly AL,York P,Coates PD,Paradkar A.Cocrystalization and simultaneous agglomeration using hot melt extrusion.Pharm Res 2010;27(12):2725-33.
[31]Brough C,Williams RO 3rd.Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery.Int J Pharm 2013;453(1):157-66.
[32]Hasa D,Voinovich D,Perissutti B,et al.Reduction of melting temperature and enthalpy of drug crystals:theoretical aspects.Eur J Pharm Sci 2013;50(1):17-28.
[33]Kerr HE,Softley LK,Suresh K,Hodgkinson P,Evans IR.Structure and physicochemical characterization of a naproxen-picolinamide cocrystal.Acta Crystallogr C Struct Chem 2017;73(Pt 3):168-75.
[34]Hecq J,Deleers M,Fanara D,et al.Preparation and in vitro/in vivo evaluation of nano-sized crystals for dissolution rate enhancement of ucb-35440-3,a highly dosed poorly water-soluble weak base.Eur J Pharm Biopharm2006;64(3):360-8.
[35]Gao L,Liu G,Ma J,et al.Drug nanocrystals:In vivo performances.J Control Release 2012;160(3):418-30.
[36]Shegokar R,Muller RH.Nanocrystals:industrially feasible multifunctional formulation technology for poorly soluble actives.Int J Pharm 2010;399(1-2):129-39.
[37]Tu L,Yi Y,Wu W,et al.Effects of particle size on the pharmacokinetics of puerarin nanocrystals and microcrystals after oral administration to rat.Int J Pharm2013;458(1):135-40.
[38]Akao T,Sato K,Hanada M.Hepatic contribution to a marked increase in the plasma concentration of baicalin after oral administration of its aglycone,baicalein,in multidrug resistance-associated protein 2-deficient rat.Biol Pharm Bull2009;32(12):2079-82.
[39]Zhang L,Lin G,Chang Q,Zuo Z.Role of intestinal first-pass metabolism of baicalein in its absorption process.Pharm Res2005;22(7):1050-8.
[40]Kang MJ,Ko GS,Oh DG,et al.Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin.Arch Pharm Res 2014;37(3):371-8.
[41]Wang J,Pang Q,Cen W,Zhu P,Xu Y.Simultaneous determination of ten active constituents of Yankening Capsule in rat plasma by ultra high performance liquid chromatography with tandem mass spectrometry.JChromatogr B Analyt Technol Biomed Life Sci2015;978-979:43-53.
[42]Qian P,Zhang YB,Yang YF,Xu W,Yang XW.Pharmacokinetics studies of 12 alkaloids in rat plasma after oral administration of Zuojin and Fan-Zuojin formulas.Molecules 2017;22(2):214.
[43]Alam MA,Al-Jenoobi FI,Al-mohizea AM.Commercially bioavailable proprietary technologies and their marketed products.Drug Discov Today 2013;18(19-20):936-49.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |