过饱和药物递送系统的研究与应用进展
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摘要
改善药物的溶解与溶出是药物制剂开发过程中面临的重要挑战。过饱和药物递送系统是近来发展的改善药物溶出和吸收的一种有效方法。综述了过饱和药物递送系统在制剂发展中的应用和形成过饱和药物递送系统过程中采用的不同类型的沉淀抑制剂及其机制,并总结了评估过饱和的体外测定方法,旨在为将难溶性药物合理设计成过饱和药物递送系统提供参考和研究思路。
Improving drug solubility and dissolution remains an important challenge in the development of pharmaceutical formulations.Supersaturating drug delivery system(SDDS) is one of the effective methods recently developed to improve drug dissolution and absorption.This paper reviewed the application of SDDS in formulation development, the different types of precipitation inhibitors used in the formation of SDDS and their mechanisms, as well as in vitro assays to evaluate supersaturation, providing reference and ideas for the rational design of SDDS for poorly water-soluble drugs.
Improving drug solubility and dissolution remains an important challenge in the development of pharmaceutical formulations.Supersaturating drug delivery system(SDDS) is one of the effective methods recently developed to improve drug dissolution and absorption.This paper reviewed the application of SDDS in formulation development, the different types of precipitation inhibitors used in the formation of SDDS and their mechanisms, as well as in vitro assays to evaluate supersaturation, providing reference and ideas for the rational design of SDDS for poorly water-soluble drugs.
引文
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[2]Bavishi D D,Borkhataria C H.Spring and parachute:how cocrystals enhance solubility[J].Prog Cryst Growth Ch,2016,62(3):1-8.
[3]Nanjwade B K,Patel D J,Udhani R A,et al.Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs[J].Sci Pharm,2011,79(4):705-727.
[4]El Maghraby G M.Self-microemulsifying and microemulsion systems for transdermal delivery of indomethacin:effect of phase transition[J].Colloids Surf B Biointerfaces,2010,75(2):595-600.
[5]Urbanrtz N A,Lippold B C.Solid dispersions of nimodipine and polyethylene glycol 2000:dissolution properties and physico-chemical characterisation[J].Eur J Pharm Biopharm,2005,59(1):107-118.
[6]Tsunashima D,Yamashita K,Ogawara K I,et al.Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method[J].J Pharm Pharmacol,2016,68(3):316-323.
[7]Pinto J M O,Le?o A F,Riekes M K,et al.HPMCAS as an effective precipitation inhibitor in amorphous solid dispersions of the poorly soluble drug candesartan cilexetil[J].Carbohyd Polym,2018,184:199-206.
[8]Knopp M M,Olesen N E,Holm P,et al.Influence of polymer molecular weight on drug-polymer solubility:a comparison between experimentally determined solubility in PVP and prediction derived from solubility in monomer[J].J Pharm Sci,2015,104(9):2905-2912.
[9]Reginald-opara J N,Attama A,Ofokansi K,et al.Molecular interaction between glimepiride and Soluplus-PEG 4000 hybrid based solid dispersions:characterisation and anti-diabetic studies[J].Int J Pharm,2015,496(2):741-750.
[10]Overhoff K A,Mcconville J T,Yang W,et al.Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing[J].Pharm Res,2008,25(1):167-175.
[11]Abdel-Mottaleb M M,Neumann D,Lamprecht A.Lipid nanocapsules for dermal application:a comparative study of lipid-based versus polymer-based nanocarriers[J].Eur J Pharm Biopharm,2011,79(1):36-42.
[12]Rubbens J,Brouwers J,Tack J,et al.Gastrointestinal dissolution,supersaturation and precipitation of the weak base indinavir in healthy volunteers[J].Eur J Pharm Biopharm,2016,109:122-129.
[13]Nielsen L H,Gordon S,Holm R,et al.Preparation of an amorphous sodium furosemide salt improves solubility and dissolution rate and leads to a faster Tmax after oral dosing to rats[J].Eur J Pharm Biopharm,2013,85(3):942-951.
[14]Kleeb S,Jiang X,Frei P,et al.FimH antagonists:phosphate prodrugs improve oral bioavailability[J].J Med Chem,2016,59(7):3163-3182.
[15]Subedi R K,Oh S Y,Chun M K,et al.Recent advances in transdermal drug delivery[J].Arch Pharm Res,2010,33(3):339-351.
[16]Li S,Pollock-Dove C,Dong L C,et al.Enhanced bioavailability of a poorly water-soluble weakly basic compound using a combination approach of solubilization agents and precipitation inhibitors:a case study[J].Mol Pharm,2012,9(5):1100-1108.
[17]Patel D D,Anderson B D.Effect of precipitation inhibitors on indomethacin supersaturation maintenance:mechanisms and modeling[J].Mol Pharm,2014,11(5):1489-1499.
[18]Jung H J,Ahn H I,Park J Y,et al.Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate[J].Int J Biol Macromol,2016,83:282-287.
[19]Weerapol Y,Tubtimsri S,Jansakul C,et al.Improved dissolution of Kaempferia parviflora extract for oral administration by preparing solid dispersion via solvent evaporation[J].Asian J Pharm Sci,2017,12(2):124-133.
[20]Seto Y,Morizane C,Ueno K,et al.Supersaturable self-emulsifying drug delivery system of krill oil with improved oral absorption and hypotriglyceridemic function[J].J Agric Food Chem,2018,66(21):5352-5358.
[21]Salimi A,Sharif Makhmal Zadeh B,Hemati A A,et al.Design and evaluation of self-emulsifying drug delivery system(SEDDS)of carvedilol to improve the oral absorption[J].Jundishapur J Nat Pharm Prod,2014,9(3):e16125.Doi:10.17795/jjnpp-16125.
[22]Bi M,Kyad A,Kiang Y H,et al.Enhancing and sustaining AMG 009dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation[J].AAPS Pharmscitech,2011,12(4):1466.Doi:10.1208/s12249-011-9679-x.
[23]Lee D R,Ho M J,Choi Y W,et al.A polyvinylpyrrolidone-based supersaturable self-emulsifying drug delivery system for enhanced dissolution of cyclosporine A[J].Polymers,2017,9(4):124.Doi:10.3390/polym9040124.
[24]Chen Z Q,Liu Y,Zhao J H,et al.Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable selfmicroemulsifying drug delivery system[J].Int J Nanomed,2012,7:1115-1125.
[25]Fornells E,Fuguet E,Ma?éM,et al.Effect of vinylpyrrolidone polymers on the solubility and supersaturation of drugs;a study using the Cheqsol method[J].Eur J Pharm Sci,2018,117:227-235.
[26]Knopp M M,Nguyen J H,Becker C,et al.Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions[J].Eur JPharm Biopharm,2016,101:145-151.
[27]Wang C,Tong Q,Hou X,et al.Enhancing bioavailability of dihydromyricetin through inhibiting precipitation of soluble cocrystals by a crystallization inhibitor[J].Cryst Growth Des,2016,16(9):5030-5039.
[28]Brouwers J,Vermeire K,Grammen C,et al.Early identification of availability issues for poorly water-soluble microbicide candidates in biorelevant media:a case study with saquinavir[J].Antiviral Res,2011,91(2):217-223.
[29]Xie T,Taylor L S.Dissolution performance of high drug loading celecoxib amorphous solid dispersions formulated with polymer combinations[J].Pharm Res,2016,33(3):739-750.
[30]Yamashita T,Ozaki S,Kushida I.Solvent shift method for antiprecipitant screening of poorly soluble drugs using biorelevant medium and dimethyl sulfoxide[J].Int J Pharm,2011,419(1/2):170-174.
[31]Saal W,Wyttenbach N,Alsenz J,et al.The quest for exceptional drug solubilization in diluted surfactant solutions and consideration of residual solid state[J].Eur J Pharm Sci,2018,111:96-103.
[32]Mullertz A,Ogbonna A,Ren S,et al.New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs[J].J Pharm Pharmacol,2010,62(11):1622-1636.
[33]Chaudhari S P,Dugar R P.Application of surfactants in solid dispersion technology for improving solubility of poorly water soluble drugs[J].JDrug Deliv Sci Tec,2017,41:68-77.
[34]Beig A,Fine-Shamir N,Porat D,et al.Concomitant solubilitypermeability increase:Vitamin E TPGS vs.amorphous solid dispersion as oral delivery systems for etoposide[J].Eur J Pharm Biopharm,2017,121:97-103.
[35]Brewster M E,Vandecruys R,Peeters J,et al.Comparative interaction of 2-hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin with itraconazole:phase-solubility behavior and stabilization of supersaturated drug solutions[J].Eur J Pharm Sci,2008,34(2):94-103.
[36]Mura P.Analytical techniques for characterization of cyclodextrin complexes in the solid state:a review[J].J Pharm Biomed,2015,113:226-238.
[37]Li N,Wang N,Wu T,et al.Preparation of curcumin-hydroxypropyl-β-cyclodextrin inclusion complex by cosolvency-lyophilization procedure to enhance oral bioavailability of the drug[J].Drug Dev Ind Pharm,2018,44(12):1966-1974.
[38]Brewster M E,Loftsson T.Cyclodextrins as pharmaceutical solubilizers[J].Adv Drug Deliv Rev,2007,59(7):645-666.
[39]Kuldipkumar A,Kwon G S,Zhang G G Z.Determining the growth mechanism of tolazamide by induction time measurement[J].Cryst Growth Des,2007,7(2):234-242.
[40]Lindfors S L,Forssén S,Westergren J,et al.Nucleation and crystal growth in supersaturated solutions of a model drug[J].J Colloid Interf Sci,2008,325(2):404-413.
[41]Gao P,Akrami A,Alvarez F,et al.Characterization and optimization of AMG 517 supersaturatable self-emulsifying drug delivery system(S-SEDDS)for improved oral absorption[J].J Pharm Sci,2009,98(2):516-528.
[42]Raghavan S L,Trividic A,Davis A F,et al.Crystallization of hydrocortisone acetate:influence of polymers[J].Int J Pharm,2001,212(2):213-221.
[43]Raut S,Atef E.Characterization of self-emulsifying drug delivery systems using in situ Raman spectroscopy to study the precipitation inhibition mechanism of poorly water-soluble drugs[J].J Pharm Innov,2018,1:1-11.
[44]Xie S,Poornachary S K,Chow P S,et al.Direct precipitation of micronsize salbutamol sulfate:new insights into the action of surfactants and polymeric additives[J].Cryst Growth Des,2010,10(8):3363-3371.
[45]Balani P N,Wong S Y,Ng W K.Influence of polymer content on stabilizing milled amorphous salbutamol sulphate[J].Int J Pharm,2010,391(1):125-136.
[46]Yani Y,Chow P S,Tan R B.Molecular simulation study of the effect of various additives on salbutamol sulfate crystal habit[J].Mol Pharm,2011,8(5):1910-1918.
[47]Ilevbare G A,Liu H,Edgar K J,et al.Maintaining supersaturation in aqueous drug solutions:impact of different polymers on induction times[J].Cryst Growth Des,2013,13(2):740-751.
[48]Dai W G,Dong L C,Li S,et al.Combination of pluronic/vitamin ETPGS as a potential inhibitor of drug precipitation[J].Int J Pharm,2008,355(1):31-37.
[49]Rasenack N,Hartenhauer H,Muller B W.Microcrystals for dissolution rate enhancement of poorly water-soluble drugs[J].Int J Pharm,2003,254(2):137-145.
[50]Zimmermann A,Millqvist-fureby A,Elema M R,et al.Adsorption of pharmaceutical excipients onto microcrystals of siramesine hydrochloride:effects on physicochemical properties[J].Eur J Pharm Biopharm,2009,71(1):109-116.
[51]Schram C J,Taylor L S,Beaudoin S P.Influence of polymers on the crystal growth rate of felodipine:correlating adsorbed polymer surface coverage to solution crystal growth inhibition[J].Langmuir,2015,31(41):11279-11287.
[52]Patel D D,Anderson B D.Adsorption of polyvinylpyrrolidone and its impact on maintenance of aqueous supersaturation of indomethacin via crystal growth inhibition[J].J Pharm Sci,2015,104(9):2923-2933.
[53]Kestur U S,Lee H,Santiago D,et al.Effects of the molecular weight and concentration of polymer additives,and temperature on the melt crystallization kinetics of a small drug molecule[J].Cryst Growth Des,2010,10(8):3585-3595.
[54]Dinunzio J C,Miller D A,Yang W,et al.Amorphous compositions using concentration enhancing polymers for improved bioavailability of itraconazole[J].Mol Pharm,2008,5(6):968-980.
[55]Bevernage J,Hens B,Brouwers J,et al.Supersaturation in human gastric fluids[J].Eur J Pharm Biopharm,2012,81(1):184-189.
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