口服固体制剂的体外溶出试验及体内外相关性研究进展
摘要
目的:为口服固体制剂的体外溶出试验和体内外相关性(IVIVC)研究的进一步开展提供参考。方法:以"体外溶出试验""体内外相关性""滞后时间""时间校正因子""Dissolution test""IVIVC""Lag time""Time scaling"等为关键词,组合检索中国知网、PubMed、Elsevier、Springer等数据库中收录的1990年1月-2017年12月期间发表的相关研究文献,结合笔者自身的研究经验和认识,进行归纳和总结,重点探讨了不同分级IVIVC尤其是A级IVIVC的建立方法。结果与结论:共获得有效文献39篇。影响口服固体制剂在体内吸收的主要限制因素为药物活性成分的溶出和跨膜吸收性质,当前的IVIVC主要建立在药物体内吸收符合胃排空或溶出限速特征的基本前提下。与口服固体制剂的体内药动学研究相比,其体外溶出研究尚未实现严格的标准化,为使体外溶出试验与体内溶出/吸收过程具有更好的相关性,生物相关介质和仿生溶出系统等将是今后的发展方向。常见的各级IVIVC中,A级IVIVC可以提供最多的信息,优先推荐建立和使用A级IVIVC,此时药物的体外溶出行为往往可以准确反映其体内吸收过程;其次是多重C级以及B级、C级和D级IVIVC。而随着仿生溶出系统和计算机数据拟合技术等的发展,将来的IVIVC研究并不会局限于缓控释制剂或生物药剂学分类属Ⅱ类药物的速释制剂,可能会有更多关于生物药剂学分类属Ⅲ、Ⅳ类药物的IVIVC研究。
引文
[1]EMAMI J.In vitro-in vivo correlation:from theory to applications[J].J Pharm Pharm Sci,2006,9(2):169-189.
[2]CARDOT JM,BEYSSAC E,ALRIC M.In vitro-in vivo correlation:importance of dissolution in IVIVC[J].Dissol Technol,2007,14(1):15-19.
[3]BROWN CK,CHOKSHI HP,NICKERSON B,et al.Dissolution testing of poorly soluble compounds[J].Pharm Tech,2004,28(12):56-65.
[4]SIRISUTH N,EDDINGTON ND.In vitro-in vivo correlation,definitions and regulatory guidance[J].Inter J Gener Drugs,2002,2:1-11.
[5]ALMUKAINZI M,BOU-CHACRA NA,WALKER RB,et al.Biorelevant dissolution testing[M].Hoboken:John Wiley&Sons,Inc.,2014:335-365.
[6]MARROUM P.Role of In vitro-in vivo correlations in drug development[J].Dissol Technol,2015,22(2):50-56.
[7]TSUME Y,MUDIE DM,LANGGUTH P,et al.The Biopharmaceutics classification system:subclasses for in vivo predictive dissolution(IPD)methodology and IVIVC[J].Eur J Pharm Sci,2014,57(1):152-163.
[8]HARDIKAR S,BHOSALE AV,BUDHAWANT RN.Establishment of in vivo-in vitro correlation:a cogent strategy in product development process[J].Indian J Pharm Educ,2014,48(4):66-73.
[9]United States Pharmacopeial Convention.USP40-NF35[S].2016:588-598、1277-1288.
[10]GARBACZ G,KO?ODZIEJ B,KOZIOLEK M,et al.A dynamic system for the simulation of fasting luminal p Hgradients using hydrogen carbonate buffers for dissolution testing of ionisable compounds[J].Eur J Pharm Sci,2014,51(1):224-231.
[11]LOCHER K,BORGHARDT JM,FRANK KJ,et al.Evolution of a mini-scale biphasic dissolution model:impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics[J].Eur J Pharm Biopharm,2016,105:166-175.
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[14]HAMED R,AWADALLAH A,SUNOQROT S,et al.p H-dependent solubility and dissolution behavior of carvedilol-case example of a weakly basic BCS classⅡdrug[J].AAPS Pharm Sci Tech,2016,17(2):418-426.
[15]CASCONE S,LAMBERTI G,MARRA F,et al.Gastrointestinal behavior and ADME phenomena:I.In vitro simulation[J].J Drug Deliv Sci Tec,2016,(35):272-283.
[16]JANTRATID E,DE MAIO V,RONDA E,et al.Application of biorelevant dissolution tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form[J].Eur J Pharm Sci,2009,37(3):434-441.
[17]李自强,何新,刘昌孝.基于胃肠道生理驱动的药物溶出/透过特征同步评价技术研究进展[J].药学学报,2016,51(10):1540-1550.
[18]SCHNORR SL,CRITTENDEN AN,VENEMA K,et al.Assessing digestibility of Hadza tubers using a dynamic in-vitro model[J].Am J Phys Anthropol,2015,158(3):371-385.
[19]VAN DONGEN AJ.Good clinical practice,a transparent way of life:a review[J].Comput Med Imag Grap,2001,25(2):213-216.
[20]SUAREZ-SHARP S,LI M,DUAN J,et al.Regulatory experience with in vivo in vitro correlations(IVIVC)in new drug applications[J].AAPS J,2016,18(6):1379-1390.
[21]CARDOT JM,BEYSSAC E.In vitro/in vivo correlations:scientific implications and standardisation[J].Eur J Drug Metab Pharmacokinet,1993,18(1):113-120.
[22]NGUYEN MA,FLANAGAN T,BREWSTER M,et al.A survey on IVIVC/IVIVR development in the pharmaceutical industry-past experience and current perspectives[J].Eur J Pharm Sci,2017,102:1-13.
[23]TANG M,HU P,HUANG S,et al.Development of an extended-release formulation for apremilast and a level A in vitro-in vivo correlation study in beagle dogs[J].Chem Pharm Bull,2016,64(11):1607-1615.
[24]CARDOT JM,DAVIT BM.In vitro-in vivo correlations:tricks and traps[J].AAPS J,2012,14(3):491-499.
[25]SCHLIECKER G,SCHMIDT C,FUCHS S,et al.In vitro and in vivo correlation of buserelin release from biodegradable implants using statistical moment analysis[J].J Control Release,2004,94(1):25-37.
[26]LAXMAN TS,DURGAPRASAD Y,TIRGAR HK,et al.Development and validation of an in vitro and in vivo correlation model in rabbit for topiramate extended release capsules[J].Indian J Pharm Sci,2017,78(6):732-740.
[27]JAIN R,S IYER S,RADHAKRISHNAN P,et al.Development and validation of level a in vitro-in vivo correlation for extended release tablets of lamotrigine[J].Curr Bioact Compd,2016,12(4):289-296.
[28]FDA.Guidance for industry:extended release oral dosage forms:development,evaluation,and application of in vitro/in vivo correlations[EB/OL].[2017-11-13].https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm0702.pdf.
[29]HERMANS A,ABEND AM,KESISOGLOU F,et al.Approaches for establishing clinically relevant dissolution specifications for immediate release solid oral dosage forms[J].AAPS J,2017,19(6):1537-1549.
[30]SHEN J,BURGESS DJ.In vitro-in vivo correlation for complex non-oral drug products:where do we stand?[J].J Controll Release,2015,219:644-651.
[31]KAUR P,JIANG X,DUAN J,et al.Applications of in vitro-in vivo correlations in generic drug development:case studies[J].AAPS J,2015,17(4):1035-1039.
[32]KUMAR V,KHURANA LK,AHMAD S,et al.Application of assumed IVIVC in product life cycle management:a case study of trimetazidine dihydrochloride extended release tablet[J].J Bioequiv Availab,2013,5(1):6-15.
[33]VAN BUSKIRK GA,SHAH V,YACOBI A,et al.PQRI workshop report:application of IVIVC in formulation development[J].Dissol Technol,2014,21(2):51-59.
[34]HASSAN HA,CHAROO NA,ALI AA,et al.Establishment of a bioequivalence-indicating dissolution specification for candesartan cilexetil tablets using a convolution model[J].Dissol Technol,2015,22(1):36-43.
[35]KOSTEWICZ ES,AARONS L,BERGSTRAND M,et al.PBPK models for the prediction of in vivo performance of oral dosage forms[J].Eur J Pharm Sci,2014,57(1):300-321.
[36]OTSUKA K,SHONO Y,DRESSMAN J.Coupling biorelevant dissolution methods with physiologically based pharmacokinetic modelling to forecast in-vivo performance of solid oral dosage forms[J].J Pharm Pharmacol,2013,65(7):937-952.
[37]CARDOT JM,TOMIC I.In vitro in vivo correlation basis and application to slow release injectable formulation,a review[J].FARMACIA,2015,63(6):781-791.
[38]PATEL H,JOSHI A,JOSHI A,et al.Transdermal delivery of etoposide phosphateⅡ:in vitro in vivo correlations(IVIVC)[J].J Pharm Sci,2016,105(7):2139-2145.
[39]YU A,JACKSON T,TSUME Y,et al.Mechanistic fluid transport model to estimate gastrointestinal fluid volume and its dynamic change over time[J].AAPS J,2017,19(6):1682-1690.
[2]CARDOT JM,BEYSSAC E,ALRIC M.In vitro-in vivo correlation:importance of dissolution in IVIVC[J].Dissol Technol,2007,14(1):15-19.
[3]BROWN CK,CHOKSHI HP,NICKERSON B,et al.Dissolution testing of poorly soluble compounds[J].Pharm Tech,2004,28(12):56-65.
[4]SIRISUTH N,EDDINGTON ND.In vitro-in vivo correlation,definitions and regulatory guidance[J].Inter J Gener Drugs,2002,2:1-11.
[5]ALMUKAINZI M,BOU-CHACRA NA,WALKER RB,et al.Biorelevant dissolution testing[M].Hoboken:John Wiley&Sons,Inc.,2014:335-365.
[6]MARROUM P.Role of In vitro-in vivo correlations in drug development[J].Dissol Technol,2015,22(2):50-56.
[7]TSUME Y,MUDIE DM,LANGGUTH P,et al.The Biopharmaceutics classification system:subclasses for in vivo predictive dissolution(IPD)methodology and IVIVC[J].Eur J Pharm Sci,2014,57(1):152-163.
[8]HARDIKAR S,BHOSALE AV,BUDHAWANT RN.Establishment of in vivo-in vitro correlation:a cogent strategy in product development process[J].Indian J Pharm Educ,2014,48(4):66-73.
[9]United States Pharmacopeial Convention.USP40-NF35[S].2016:588-598、1277-1288.
[10]GARBACZ G,KO?ODZIEJ B,KOZIOLEK M,et al.A dynamic system for the simulation of fasting luminal p Hgradients using hydrogen carbonate buffers for dissolution testing of ionisable compounds[J].Eur J Pharm Sci,2014,51(1):224-231.
[11]LOCHER K,BORGHARDT JM,FRANK KJ,et al.Evolution of a mini-scale biphasic dissolution model:impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics[J].Eur J Pharm Biopharm,2016,105:166-175.
[12]REPPAS C,VERTZONI M.Biorelevant in-vitro performance testing of orally administered dosage forms[J].J Pharm Pharmacol,2012,64(7):919-930.
[13]SJ?GREN E,ABRAHAMSSON B,AUGUSTIJNS P,et al.In vivo methods for drug absorption-comparative physiologies,model selection,correlations with in vitro methods(IVIVC),and applications for formulation/API/excipient characterization including food effects[J].Eur J Pharm Sci,2014,57(1):99-151.
[14]HAMED R,AWADALLAH A,SUNOQROT S,et al.p H-dependent solubility and dissolution behavior of carvedilol-case example of a weakly basic BCS classⅡdrug[J].AAPS Pharm Sci Tech,2016,17(2):418-426.
[15]CASCONE S,LAMBERTI G,MARRA F,et al.Gastrointestinal behavior and ADME phenomena:I.In vitro simulation[J].J Drug Deliv Sci Tec,2016,(35):272-283.
[16]JANTRATID E,DE MAIO V,RONDA E,et al.Application of biorelevant dissolution tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form[J].Eur J Pharm Sci,2009,37(3):434-441.
[17]李自强,何新,刘昌孝.基于胃肠道生理驱动的药物溶出/透过特征同步评价技术研究进展[J].药学学报,2016,51(10):1540-1550.
[18]SCHNORR SL,CRITTENDEN AN,VENEMA K,et al.Assessing digestibility of Hadza tubers using a dynamic in-vitro model[J].Am J Phys Anthropol,2015,158(3):371-385.
[19]VAN DONGEN AJ.Good clinical practice,a transparent way of life:a review[J].Comput Med Imag Grap,2001,25(2):213-216.
[20]SUAREZ-SHARP S,LI M,DUAN J,et al.Regulatory experience with in vivo in vitro correlations(IVIVC)in new drug applications[J].AAPS J,2016,18(6):1379-1390.
[21]CARDOT JM,BEYSSAC E.In vitro/in vivo correlations:scientific implications and standardisation[J].Eur J Drug Metab Pharmacokinet,1993,18(1):113-120.
[22]NGUYEN MA,FLANAGAN T,BREWSTER M,et al.A survey on IVIVC/IVIVR development in the pharmaceutical industry-past experience and current perspectives[J].Eur J Pharm Sci,2017,102:1-13.
[23]TANG M,HU P,HUANG S,et al.Development of an extended-release formulation for apremilast and a level A in vitro-in vivo correlation study in beagle dogs[J].Chem Pharm Bull,2016,64(11):1607-1615.
[24]CARDOT JM,DAVIT BM.In vitro-in vivo correlations:tricks and traps[J].AAPS J,2012,14(3):491-499.
[25]SCHLIECKER G,SCHMIDT C,FUCHS S,et al.In vitro and in vivo correlation of buserelin release from biodegradable implants using statistical moment analysis[J].J Control Release,2004,94(1):25-37.
[26]LAXMAN TS,DURGAPRASAD Y,TIRGAR HK,et al.Development and validation of an in vitro and in vivo correlation model in rabbit for topiramate extended release capsules[J].Indian J Pharm Sci,2017,78(6):732-740.
[27]JAIN R,S IYER S,RADHAKRISHNAN P,et al.Development and validation of level a in vitro-in vivo correlation for extended release tablets of lamotrigine[J].Curr Bioact Compd,2016,12(4):289-296.
[28]FDA.Guidance for industry:extended release oral dosage forms:development,evaluation,and application of in vitro/in vivo correlations[EB/OL].[2017-11-13].https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm0702.pdf.
[29]HERMANS A,ABEND AM,KESISOGLOU F,et al.Approaches for establishing clinically relevant dissolution specifications for immediate release solid oral dosage forms[J].AAPS J,2017,19(6):1537-1549.
[30]SHEN J,BURGESS DJ.In vitro-in vivo correlation for complex non-oral drug products:where do we stand?[J].J Controll Release,2015,219:644-651.
[31]KAUR P,JIANG X,DUAN J,et al.Applications of in vitro-in vivo correlations in generic drug development:case studies[J].AAPS J,2015,17(4):1035-1039.
[32]KUMAR V,KHURANA LK,AHMAD S,et al.Application of assumed IVIVC in product life cycle management:a case study of trimetazidine dihydrochloride extended release tablet[J].J Bioequiv Availab,2013,5(1):6-15.
[33]VAN BUSKIRK GA,SHAH V,YACOBI A,et al.PQRI workshop report:application of IVIVC in formulation development[J].Dissol Technol,2014,21(2):51-59.
[34]HASSAN HA,CHAROO NA,ALI AA,et al.Establishment of a bioequivalence-indicating dissolution specification for candesartan cilexetil tablets using a convolution model[J].Dissol Technol,2015,22(1):36-43.
[35]KOSTEWICZ ES,AARONS L,BERGSTRAND M,et al.PBPK models for the prediction of in vivo performance of oral dosage forms[J].Eur J Pharm Sci,2014,57(1):300-321.
[36]OTSUKA K,SHONO Y,DRESSMAN J.Coupling biorelevant dissolution methods with physiologically based pharmacokinetic modelling to forecast in-vivo performance of solid oral dosage forms[J].J Pharm Pharmacol,2013,65(7):937-952.
[37]CARDOT JM,TOMIC I.In vitro in vivo correlation basis and application to slow release injectable formulation,a review[J].FARMACIA,2015,63(6):781-791.
[38]PATEL H,JOSHI A,JOSHI A,et al.Transdermal delivery of etoposide phosphateⅡ:in vitro in vivo correlations(IVIVC)[J].J Pharm Sci,2016,105(7):2139-2145.
[39]YU A,JACKSON T,TSUME Y,et al.Mechanistic fluid transport model to estimate gastrointestinal fluid volume and its dynamic change over time[J].AAPS J,2017,19(6):1682-1690.