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Article(id=1195816329925144946, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195816324862624679, articleNumber=1001-2494(2024)24-2343-11, orderNo=null, doi=10.11669/cpj.2024.24.007, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1709049600000, receivedDateStr=2024-02-28, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1763034430246, onlineDateStr=2025-11-13, pubDate=1734796800000, pubDateStr=2024-12-22, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763034430246, onlineIssueDateStr=2025-11-13, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763034430246, creator=13701087609, updateTime=1763034430246, updator=13701087609, issue=Issue{id=1195816324862624679, tenantId=1146029695717560320, journalId=1190317699101192196, year='2024', volume='59', issue='24', pageStart='2299', pageEnd='2406', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763034429040, creator=13701087609, updateTime=1763034724390, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1195817563738390939, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195816324862624679, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1195817563738390940, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195816324862624679, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2343, endPage=2353, ext={EN=ArticleExt(id=1195816330294243699, articleId=1195816329925144946, tenantId=1146029695717560320, journalId=1190317699101192196, language=EN, title=Preparation and Evaluation of Fenofibrate Self-microemulsifying Drug Delivery System, columnId=null, journalTitle=Chinese Pharmaceutical Journal, columnName=null, runingTitle=null, highlight=null, articleAbstract=

OBJECTIVE In order to improve the solubility and dissolution of the insoluble drug fenofibrate (FNB) optimize, the prescription of the self-microemulsifying drug delivery system (SMEDDS) was optimized and its quality was evaluated. METHODS The prescription composition and proportion range of SMEDDS were determined by the solubility experiment, compatibility test and pseudoternary phase diagram. Star point design-response surface methodology was used to further optimize the formulation of fenofibrate self-microemulsifying drug delivery system (FNB-SMEDDS) by using solubility, average particle size and polydispersity index (PDI) as evaluation indicators. The physical and chemical properties, and preliminary stability of FNB-SMEDDS were evaluated. RESULTS The optimal prescription of FNB-SMEDDS was ethyl oleate (EO) 22.86% as oil phase, polyoxyethylene (40) hydrogenated castor oil (cremophor RH40) 51.07% as surfactant, diethylene glycol monoethyl ether (transcutol HP) 26.07% as co-surfactant. The obtained FNB-SMEDDS was uniform and transparent. The FNB-SMEDDS was self-emulsified in water with average particle size of (39.29±0.45) nm, PDI of (0.11±0.01), Zeta potential of (-7.7±0.9) mV, drug loading rate of 15 mg·g-1, encapsulation rate of (95.11±0.26)%, and emulsification time of (56.03±1.65) s. Stability experiments showed that after being stored at room temperature in the dark for 30 days, there was no significant change in its index components and appearance properties, indicating good stability. Compared with FNB API, FNB-SMEDDS significantly improved the in vitro dissolution of FNB. The cumulative release rates in water, pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution for 120 min were (97.68±0.61)%, (92.23±4.07)% and (93.65±2.25)%, respectively. CONCLUSION FNB-SMEDDS has good appearance, high emulsification efficiency. It can significantly improve in vitro dissolution of the drug, and is expected to improve the in vivo bioavailability of FNB.

, correspAuthors=Wenjun ZHANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Jiangwei LÜ, Jingjing JIANG, Wei CHEN, Xueying ZHAO, Wenjun ZHANG, Youpeng QU), CN=ArticleExt(id=1195816655843537820, articleId=1195816329925144946, tenantId=1146029695717560320, journalId=1190317699101192196, language=CN, title=非诺贝特自微乳给药系统的制备及质量评价, columnId=1190352405612040510, journalTitle=中国药学杂志, columnName=论著, runingTitle=null, highlight=null, articleAbstract=

目的 提高难溶性药物非诺贝特(fenofibrate,FNB)的溶解度及溶出度,优化自微乳给药系统(self-microemulsifying drug delivery system, SMEDDS)的处方并进行质量评价。方法 在溶解度考察、配伍实验与伪三元相图的基础上,确定SMEDDS处方组成及比例范围。以溶解度、平均粒径及多分散系数(polydispersity index, PDI)为评价指标,采用星点设计-效应面法进一步优化非诺贝特自微乳(FNB-SMEDDS)的处方,并对其理化性质及初步稳定性等进行质量评价。结果 FNB-SMEDDS最优处方为质量分数22.86%的油酸乙酯(ethyl oleate,EO)为油相,质量分数51.07%的聚氧乙烯(40)氢化蓖麻油(cremophor RH40)为表面活性剂,质量分数26.07%的二乙二醇单乙基醚(transcutol HP)为助表面活性剂。制备的自微乳外观均一透明,水中自乳化后平均粒径为(39.29±0.45) nm,PDI为(0.11±0.01),Zeta电位为(-7.7±0.9) mV,载药量为15 mg·g-1,包封率为(95.11±0.26)%,乳化时间为(56.03±1.65)s。稳定性实验显示,FNB-SMEDDS室温避光保存30 d后其指标成分及外观性状均无明显变化,稳定性良好。与FNB原料药相比,FNB-SMEDDS显著提高了FNB的体外溶出度,在水、pH 1.2盐酸溶液和pH 6.8磷酸盐缓冲液中120 min的累积释放率分别为(97.68±0.61)%、(92.23±4.07)%和(93.65±2.25)%。。结论 FNB-SMEDDS外观良好,乳化效率高,能显著提高药物的体外溶出,有望改善FNB的体内生物利用度。

, correspAuthors=张文君, authorNote=null, correspAuthorsNote=
* 张文君,女,博士,教授,硕士生导师 研究方向:新型药物传输系统 Tel:(0451)84838207
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吕江维,女,博士,副教授,硕士生导师 研究方向:新型药物传输系统

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吕江维,女,博士,副教授,硕士生导师 研究方向:新型药物传输系统

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吕江维,女,博士,副教授,硕士生导师 研究方向:新型药物传输系统

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journalName=Expert Opin Ther Targets, refType=null, unstructuredReference=VAN BILSEN M, VAN NIEUWENHOVEN F A. PPARs as therapeutic targets in cardiovascular disease[J]. Expert Opin Ther Targets, 2010, 14(10):1029-1045., articleTitle=PPARs as therapeutic targets in cardiovascular disease, refAbstract=null), Reference(id=1196081916324655862, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=61, issue=5, pageStart=494, pageEnd=504, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=SAHA M, DHIMAN S, GUPTA G D, journalName=J Chromatogr Sci, refType=null, unstructuredReference=SAHA M, DHIMAN S, GUPTA G D, et al. An investigative review for pharmaceutical analysis of fenofibrate[J]. J Chromatogr Sci, 2023, 61(5):494-504., articleTitle=An investigative review for pharmaceutical analysis of fenofibrate, refAbstract=null), Reference(id=1196081916383376119, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=1995, volume=12, issue=3, pageStart=413, pageEnd=420, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=AMIDON G L, LENNERNAS H, SHAH V P, journalName=Pharm Res, refType=null, unstructuredReference=AMIDON G L, LENNERNAS H, SHAH V P, et al. A theoretical basis for a biopharmaceutic drug classification: the correlation of in-vitro drug product dissolution and in-vivo bioavailability[J]. Pharm Res, 1995, 12(3):413-420., articleTitle=A theoretical basis for a biopharmaceutic drug classification: the correlation of in-vitro drug product dissolution and in-vivo bioavailability, refAbstract=null), Reference(id=1196081917444535032, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2011, volume=79, issue=1, pageStart=126, pageEnd=134, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=JIA Z, LIN P, XIANG Y, journalName=Eur J Pharm Biopharm, refType=null, unstructuredReference=JIA Z, LIN P, XIANG Y, et al. A novel nanomatrix system consisted of colloidal silica and pH-sensitive polymethylacrylate improves the oral bioavailability of fenofibrate[J]. Eur J Pharm Biopharm, 2011, 79(1):126-134., articleTitle=A novel nanomatrix system consisted of colloidal silica and pH-sensitive polymethylacrylate improves the oral bioavailability of fenofibrate, refAbstract=null), Reference(id=1196081917574558457, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=42, issue=3, pageStart=199, pageEnd=203, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=FENG Q Q, ZHANG T Y, LIU R, journalName=J Pharm Res(药学研究), refType=null, unstructuredReference=FENG Q Q, ZHANG T Y, LIU R, et al. Research progress of fenofibrate preparation[J]. J Pharm Res(药学研究), 2023, 42(3):199-203., articleTitle=Research progress of fenofibrate preparation, refAbstract=null), Reference(id=1196081917696193274, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2011, volume=32, issue=9, pageStart=552, pageEnd=557, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=LI F, FENG L L, YAN C, journalName=World Clin Drugs(世界临床药物), refType=null, unstructuredReference=LI F, FENG L L, YAN C. Research progress of fenofi brate formulation[J]. World Clin Drugs(世界临床药物), 2011, 32 (9): 552-557., articleTitle=Research progress of fenofi brate formulation, refAbstract=null), Reference(id=1196081917759107835, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2020, volume=5, issue=4, pageStart=1478, pageEnd=1490, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=KUMAR R, journalName=Chemistryselect, refType=null, unstructuredReference=KUMAR R. Solubility and bioavailability of fenofibrate nanoformulations[J]. Chemistryselect, 2020, 5(4):1478-1490., articleTitle=Solubility and bioavailability of fenofibrate nanoformulations, refAbstract=null), Reference(id=1196081917830411004, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2016, volume=33, issue=1, pageStart=1, pageEnd=39, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=KARWAL R, GARG T, RATH G, journalName=Crit Rev Ther Drug Carrier Sys, refType=null, unstructuredReference=KARWAL R, GARG T, RATH G, et al. Current trends in self-emulsifying drug-delivery systems (SEDDSs) to enhance the bioavailability of poorly water-soluble drugs[J]. Crit Rev Ther Drug Carrier Sys, 2016, 33(1):1-39., articleTitle=Current trends in self-emulsifying drug-delivery systems (SEDDSs) to enhance the bioavailability of poorly water-soluble drugs, refAbstract=null), Reference(id=1196081917889131261, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=12, issue=5, pageStart=1109, pageEnd=1119, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=SILBERSTEIN S, SPIERINGS E L H, KUNKEL T, journalName=Pain Therapy, refType=null, unstructuredReference=SILBERSTEIN S, SPIERINGS E L H, KUNKEL T. Celecoxib oral solution and the benefits of self-microemulsifying drug delivery systems (SMEDDS) technology: a narrative review[J]. Pain Therapy, 2023, 12(5):1109-1119., articleTitle=Celecoxib oral solution and the benefits of self-microemulsifying drug delivery systems (SMEDDS) technology: a narrative review, refAbstract=null), Reference(id=1196081918027543294, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2013, volume=50, issue=3-4, pageStart=459, pageEnd=466, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=SERMKAEW N, KETJINDA W, BOONME P, journalName=Eur J Pharm Sci, refType=null, unstructuredReference=SERMKAEW N, KETJINDA W, BOONME P, et al. Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of andrographis paniculata[J]. Eur J Pharm Sci, 2013, 50(3-4):459-466., articleTitle=Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of andrographis paniculata, refAbstract=null), Reference(id=1196081918161761023, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2014, volume=476, issue=1-2, pageStart=60, pageEnd=69, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=MAHMOUD D B, SHUKR M H, BENDAS E R, journalName=Int J Pharm, refType=null, unstructuredReference=MAHMOUD D B, SHUKR M H, BENDAS E R. In vitro and in vivo evaluation of self-nanoemulsifying drug delivery systems of cilostazol for oral and parenteral administration[J]. Int J Pharm, 2014, 476(1-2):60-69., articleTitle=In vitro and in vivo evaluation of self-nanoemulsifying drug delivery systems of cilostazol for oral and parenteral administration, refAbstract=null), Reference(id=1196081918254035712, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=42, issue=2, pageStart=126, pageEnd=129, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=JIN K, LV J, BEN Y, journalName=J Pharm Res(药学研究), refType=null, unstructuredReference=JIN K, LV J, BEN Y, et al. Research progress of solid self-microemulsion drug delivery system[J]. J Pharm Res(药学研究), 2023, 42(2):126-129,144., articleTitle=Research progress of solid self-microemulsion drug delivery system, refAbstract=null), Reference(id=1196081918342116097, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2007, volume=9, issue=3, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=PATEL A R, VAVIA P R, journalName=AAPS J, refType=null, unstructuredReference=PATEL A R, VAVIA P R. Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate[J]. AAPS J, 2007, 9(3):E344-E352., articleTitle=Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate, refAbstract=null), Reference(id=1196081918463750914, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2020, volume=15, issue=null, pageStart=2059, pageEnd=2070, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=LIU C S, CHEN L, HU Y N, journalName=Int J Nanomed, refType=null, unstructuredReference=LIU C S, CHEN L, HU Y N, et al. Self-microemulsifying drug delivery system for improved oral delivery and hypnotic efficacy of ferulic acid[J]. Int J Nanomed, 2020, 15:2059-2070., articleTitle=Self-microemulsifying drug delivery system for improved oral delivery and hypnotic efficacy of ferulic acid, refAbstract=null), Reference(id=1196081918547636995, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2009, volume=4, issue=1, pageStart=47, pageEnd=50, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=ZHANG N, ZHOU H B, QUAN D Q, journalName=Chin Med Biotechnol(中国医药生物技术), refType=null, unstructuredReference=ZHANG N, ZHOU H B, QUAN D Q. Mechanism and application of self-microemulsion drug release system to improve drug bioavailability[J]. Chin Med Biotechnol(中国医药生物技术), 2009, 4(1):47-50., articleTitle=Mechanism and application of self-microemulsion drug release system to improve drug bioavailability, refAbstract=null), Reference(id=1196081918618940164, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=58, issue=12, pageStart=1110, pageEnd=1116, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=CHEN G, QU H, XIE M, journalName=Chin Pharm J(中国药学杂志), refType=null, unstructuredReference=CHEN G, QU H, XIE M, et al. Research on prescription of eczema nanoemulsion based on pseudo ternary phase diagram method[J]. Chin Pharm J(中国药学杂志), 2023, 58(12):1110-1116., articleTitle=Research on prescription of eczema nanoemulsion based on pseudo ternary phase diagram method, refAbstract=null), Reference(id=1196081918698631941, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2021, volume=56, issue=1, pageStart=169, pageEnd=177, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=FANG Z, HUANG W, QI J, journalName=Acta Pharm Sin(药学学报), refType=null, unstructuredReference=FANG Z, HUANG W, QI J, et al. Progress on application of central composite design-response surface methodology in optimization of preparations in China[J]. Acta Pharm Sin(药学学报), 2021, 56(1):169-177., articleTitle=Progress on application of central composite design-response surface methodology in optimization of preparations in China, refAbstract=null), Reference(id=1196081918778323718, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=58, issue=11, pageStart=987, pageEnd=996, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=XU Z, ZHANG X, SU S, journalName=Chin Pharm J(中国药学杂志), refType=null, unstructuredReference=XU Z, ZHANG X, SU S, et al. Compatibility optimization and anti-inflammatory effects of salvianolic acid B and tanshinone ⅡA in protecting renal cells injured by high glucose based on star point design-response surface methodology[J]. Chin Pharm J(中国药学杂志), 2023, 58(11):987-996., articleTitle=Compatibility optimization and anti-inflammatory effects of salvianolic acid B and tanshinone ⅡA in protecting renal cells injured by high glucose based on star point design-response surface methodology, refAbstract=null), Reference(id=1196081918891569927, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=58, issue=5, pageStart=435, pageEnd=446, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=ZHANG K, FU H, WANG Y, journalName=Chin Pharm J(中国药学杂志), refType=null, unstructuredReference=ZHANG K, FU H, WANG Y, et al. Micro-porous osmotic pump and elementary osmotic pump controlled-release tablets of zalcitabine[J]. Chin Pharm J(中国药学杂志), 2023, 58(5):435-446., articleTitle=Micro-porous osmotic pump and elementary osmotic pump controlled-release tablets of zalcitabine, refAbstract=null), Reference(id=1196081918958678792, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2021, volume=52, issue=5, pageStart=1291, pageEnd=1302, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=ZHANG R, YANG B, LIAO M, journalName=Chin Tradit Herb Drugs(中草药), refType=null, unstructuredReference=ZHANG R, YANG B, LIAO M, et al. Preparation and evaluation of dihydroartemisinin self-microemulsion drug delivery system[J]. Chin Tradit Herb Drugs(中草药), 2021, 52(5):1291-1302., articleTitle=Preparation and evaluation of dihydroartemisinin self-microemulsion drug delivery system, refAbstract=null), Reference(id=1196081919088702217, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2014, volume=45, issue=22, pageStart=3256, pageEnd=3265, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=LU X, HE L, CHEN J, journalName=Chin Tradit Herb Drugs(中草药), refType=null, unstructuredReference=LU X, HE L, CHEN J, et al. Preparation and in vitro dissolution evaluation of tanshinone ⅡA for oral self-microemulsion[J]. Chin Tradit Herb Drugs(中草药), 2014, 45(22):3256-3265., articleTitle=Preparation and in vitro dissolution evaluation of tanshinone ⅡA for oral self-microemulsion, refAbstract=null), Reference(id=1196081919176782602, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2000, volume=11, issue=S2, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=POUTON C W, journalName=Eur J Pharm Sci, refType=null, unstructuredReference=POUTON C W. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems[J]. Eur J Pharm Sci, 2000, 11(S2):S93-S98., articleTitle=Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems, refAbstract=null), Reference(id=1196081919290028811, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2006, volume=29, issue=3-4, pageStart=278, pageEnd=287, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=POUTON C W, journalName=Eur J Pharm Sci, refType=null, unstructuredReference=POUTON C W. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system[J]. Eur J Pharm Sci, 2006, 29(3-4):278-287., articleTitle=Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system, refAbstract=null), Reference(id=1196081919378109196, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2023, volume=16, issue=2, pageStart=283, pageEnd=null, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=HSIEH C M, YANG T L, PUTRI A D, journalName=Pharmaceuticals, refType=null, unstructuredReference=HSIEH C M, YANG T L, PUTRI A D, et al. Application of design of experiments in the development of self-microemulsifying drug delivery systems[J]. Pharmaceuticals, 2023, 16(2):283., articleTitle=Application of design of experiments in the development of self-microemulsifying drug delivery systems, refAbstract=null), Reference(id=1196081919453606669, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2016, volume=141, issue=null, pageStart=476, pageEnd=482, url=null, language=null, rfNumber=[25], rfOrder=24, authorNames=QUAN G, WU Q, ZHANG X, journalName=Colloids Surfaces B-Biointerfaces, refType=null, unstructuredReference=QUAN G, WU Q, ZHANG X, et al. Enhancing in vitro dissolution and in vivo bioavailability of fenofibrate by solid self-emulsifying matrix combined with SBA-15 mesoporous silica[J]. Colloids Surfaces B-Biointerfaces, 2016, 141:476-482., articleTitle=Enhancing in vitro dissolution and in vivo bioavailability of fenofibrate by solid self-emulsifying matrix combined with SBA-15 mesoporous silica, refAbstract=null), Reference(id=1196081919516521230, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, doi=null, pmid=null, pmcid=null, year=2014, volume=25, issue=37, pageStart=3528, pageEnd=3532, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=LI W, SUN J, WANG R, journalName=J China Pharm(中国药房), refType=null, unstructuredReference=LI W, SUN J, WANG R. Overview and research progress of self-emulsifying drug delivery systems[J]. J China Pharm(中国药房), 2014, 25(37):3528-3532., articleTitle=Overview and research progress of self-emulsifying drug delivery systems, refAbstract=null)], funds=[Fund(id=1196081915905225459, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, awardId=MB20160087, language=CN, fundingSource=国家重点研发计划项目(MB20160087), fundOrder=null, country=null), Fund(id=1196081915968140020, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, awardId=2019CX12, language=CN, fundingSource=2019年哈尔滨商业大学青年人才专项计划项目(2019CX12), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1196081908720382629, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, xref=1, ext=[AuthorCompanyExt(id=1196081908741354150, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, companyId=1196081908720382629, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1 School of Pharmacy, Harbin University of Commerce, Harbin 150076, China), AuthorCompanyExt(id=1196081908749742759, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, companyId=1196081908720382629, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1 哈尔滨商业大学药学院, 哈尔滨 150076)]), AuthorCompany(id=1196081908925903528, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, xref=2, ext=[AuthorCompanyExt(id=1196081908934292137, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, companyId=1196081908925903528, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2 School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China), AuthorCompanyExt(id=1196081908942680746, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, companyId=1196081908925903528, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2 哈尔滨工业大学生命科学与技术学院, 哈尔滨 150080)])], figs=[ArticleFig(id=1196081911769641687, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=EN, label=Fig.1, caption=Solubility of FNB in various excipients. 37 ℃,n=3,$\bar{x}±s$, figureFileSmall=7i9bsqkAqA1G5KKjQ9149w==, figureFileBig=6NTUinYl6wuDQkhjCibI0g==, tableContent=null), ArticleFig(id=1196081911853527768, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=CN, label=图1, caption=非诺贝特(FNB)在各种辅料中的溶解度。37 ℃,n=3,$\bar{x}±s$, figureFileSmall=7i9bsqkAqA1G5KKjQ9149w==, figureFileBig=6NTUinYl6wuDQkhjCibI0g==, tableContent=null), ArticleFig(id=1196081911933219545, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=EN, label=Fig.2, caption=Pseudoternary phase diagram of blank SMEDDS

A-EO, Cremophor RH40 and Transcutol HP;B-EO, Tween 80 and Transcutol HP.

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A-油相EO、Cremophor RH40和Transcutol HP;B-EO、Tween 80和Transcutol HP。

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A-equilibrium solubility; B-average particle size; C-PDI.

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A-平衡溶解度;B-粒径;C-多分散系数(PDI)。

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Compatibility results of oil phase EO and different surfactants (Tween 20、Tween 80 and Cremophor RH 40)

, figureFileSmall=null, figureFileBig=null, tableContent=
Oil Surfactants Prescription proportion
1∶9 2∶8 3∶7 4∶6 5∶5 6∶4 7∶3
EO Tween 20 A A B C C D D
Tween 80 A A A B B C D
Cremophor RH40 A A A B B B C
), ArticleFig(id=1196081915020227308, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=CN, label=表1, caption=

油相EO与表面活性剂(Tween 20、Tween 80和Cremophor RH 40)的配伍结果

, figureFileSmall=null, figureFileBig=null, tableContent=
Oil Surfactants Prescription proportion
1∶9 2∶8 3∶7 4∶6 5∶5 6∶4 7∶3
EO Tween 20 A A B C C D D
Tween 80 A A A B B C D
Cremophor RH40 A A A B B B C
), ArticleFig(id=1196081915146056429, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=EN, label=Tab.2, caption=

Two-factor five-level CCD table

, figureFileSmall=null, figureFileBig=null, tableContent=
Factors Levels
-1.414 -1 0 1 1.414
X1(Oil/%) 10.10 13 20 27 29.90
X2(Km) 0.49 1 2.23 3.45 3.96
), ArticleFig(id=1196081915380937454, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=CN, label=表2, caption=

两因素五水平星点设计表

, figureFileSmall=null, figureFileBig=null, tableContent=
Factors Levels
-1.414 -1 0 1 1.414
X1(Oil/%) 10.10 13 20 27 29.90
X2(Km) 0.49 1 2.23 3.45 3.96
), ArticleFig(id=1196081915439657711, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=EN, label=Tab.3, caption=

Experimental design results of two-factor five-level CCD

, figureFileSmall=null, figureFileBig=null, tableContent=
No. X1(Oil/%) X2(Km) Y1(Solubility/mg·g-1) Y2(Average particle size/nm) Y3(PDI/%)
1 13.00(-1) 1.00(-1) 110.01 47.50 18.80
2 27.00(+1) 1.00(-1) 116.11 61.58 11.40
3 13.00(-1) 3.45(+1) 85.02 45.32 26.20
4 27.00(+1) 3.45(+1) 87.06 40.00 13.10
5 10.10(-1.414) 2.23(0) 91.57 46.18 23.90
6 29.90(+1.414) 2.23(0) 96.49 53.55 10.60
7 20.00(0) 0.49(-1.414) 102.64 47.52 22.40
8 20.00(0) 3.96(+1.414) 75.79 45.01 21.80
9 20.00(0) 2.23(0) 105.85 33.96 14.00
10 20.00(0) 2.23(0) 109.29 33.77 13.20
11 20.00(0) 2.23(0) 106.25 39.97 14.20
12 20.00(0) 2.23(0) 106.12 35.53 14.30
13 20.00(0) 2.23(0) 106.52 36.40 14.90
), ArticleFig(id=1196081915519349488, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=CN, label=表3, caption=

两因素五水平星点设计实验结果

, figureFileSmall=null, figureFileBig=null, tableContent=
No. X1(Oil/%) X2(Km) Y1(Solubility/mg·g-1) Y2(Average particle size/nm) Y3(PDI/%)
1 13.00(-1) 1.00(-1) 110.01 47.50 18.80
2 27.00(+1) 1.00(-1) 116.11 61.58 11.40
3 13.00(-1) 3.45(+1) 85.02 45.32 26.20
4 27.00(+1) 3.45(+1) 87.06 40.00 13.10
5 10.10(-1.414) 2.23(0) 91.57 46.18 23.90
6 29.90(+1.414) 2.23(0) 96.49 53.55 10.60
7 20.00(0) 0.49(-1.414) 102.64 47.52 22.40
8 20.00(0) 3.96(+1.414) 75.79 45.01 21.80
9 20.00(0) 2.23(0) 105.85 33.96 14.00
10 20.00(0) 2.23(0) 109.29 33.77 13.20
11 20.00(0) 2.23(0) 106.25 39.97 14.20
12 20.00(0) 2.23(0) 106.12 35.53 14.30
13 20.00(0) 2.23(0) 106.52 36.40 14.90
), ArticleFig(id=1196081915640984305, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=EN, label=Tab.4, caption=

Validation of optimized FNB-SMEDDS prescriptions by CCD-response surface methodology. n=3,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=
Factors Predicted value Measured value Deviation/%
Solubility/mg·g-1 109.13 108.87±0.58 0.24
Average particle size/nm 39.54 39.12±0.63 1.06
PDI/% 12.34 11.90±0.60 3.57
), ArticleFig(id=1196081915741647602, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816329925144946, language=CN, label=表4, caption=

星点设计-效应面法优化FNB-SMEDDS处方的验证。n=3,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=
Factors Predicted value Measured value Deviation/%
Solubility/mg·g-1 109.13 108.87±0.58 0.24
Average particle size/nm 39.54 39.12±0.63 1.06
PDI/% 12.34 11.90±0.60 3.57
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非诺贝特自微乳给药系统的制备及质量评价
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吕江维 1 , 姜京京 1 , 陈威 1 , 赵雪莹 1 , 张文君 1, * , 曲有鹏 2
中国药学杂志 | 论著 2024,59(24): 2343-2353
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中国药学杂志 | 论著 2024, 59(24): 2343-2353
非诺贝特自微乳给药系统的制备及质量评价
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吕江维1, 姜京京1, 陈威1, 赵雪莹1, 张文君1, *, 曲有鹏2
作者信息
  • 1 哈尔滨商业大学药学院, 哈尔滨 150076
  • 2 哈尔滨工业大学生命科学与技术学院, 哈尔滨 150080

    • 吕江维,女,博士,副教授,硕士生导师 研究方向:新型药物传输系统

通讯作者:

* 张文君,女,博士,教授,硕士生导师 研究方向:新型药物传输系统 Tel:(0451)84838207
Preparation and Evaluation of Fenofibrate Self-microemulsifying Drug Delivery System
Jiangwei LÜ1, Jingjing JIANG1, Wei CHEN1, Xueying ZHAO1, Wenjun ZHANG1, *, Youpeng QU2
Affiliations
  • 1 School of Pharmacy, Harbin University of Commerce, Harbin 150076, China
  • 2 School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China
出版时间: 2024-12-22 doi: 10.11669/cpj.2024.24.007
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摘要
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目的 提高难溶性药物非诺贝特(fenofibrate,FNB)的溶解度及溶出度,优化自微乳给药系统(self-microemulsifying drug delivery system, SMEDDS)的处方并进行质量评价。方法 在溶解度考察、配伍实验与伪三元相图的基础上,确定SMEDDS处方组成及比例范围。以溶解度、平均粒径及多分散系数(polydispersity index, PDI)为评价指标,采用星点设计-效应面法进一步优化非诺贝特自微乳(FNB-SMEDDS)的处方,并对其理化性质及初步稳定性等进行质量评价。结果 FNB-SMEDDS最优处方为质量分数22.86%的油酸乙酯(ethyl oleate,EO)为油相,质量分数51.07%的聚氧乙烯(40)氢化蓖麻油(cremophor RH40)为表面活性剂,质量分数26.07%的二乙二醇单乙基醚(transcutol HP)为助表面活性剂。制备的自微乳外观均一透明,水中自乳化后平均粒径为(39.29±0.45) nm,PDI为(0.11±0.01),Zeta电位为(-7.7±0.9) mV,载药量为15 mg·g-1,包封率为(95.11±0.26)%,乳化时间为(56.03±1.65)s。稳定性实验显示,FNB-SMEDDS室温避光保存30 d后其指标成分及外观性状均无明显变化,稳定性良好。与FNB原料药相比,FNB-SMEDDS显著提高了FNB的体外溶出度,在水、pH 1.2盐酸溶液和pH 6.8磷酸盐缓冲液中120 min的累积释放率分别为(97.68±0.61)%、(92.23±4.07)%和(93.65±2.25)%。。结论 FNB-SMEDDS外观良好,乳化效率高,能显著提高药物的体外溶出,有望改善FNB的体内生物利用度。

非诺贝特  /  自微乳给药系统  /  伪三元相图  /  星点设计-效应面法  /  质量评价  /  溶出度

OBJECTIVE In order to improve the solubility and dissolution of the insoluble drug fenofibrate (FNB) optimize, the prescription of the self-microemulsifying drug delivery system (SMEDDS) was optimized and its quality was evaluated. METHODS The prescription composition and proportion range of SMEDDS were determined by the solubility experiment, compatibility test and pseudoternary phase diagram. Star point design-response surface methodology was used to further optimize the formulation of fenofibrate self-microemulsifying drug delivery system (FNB-SMEDDS) by using solubility, average particle size and polydispersity index (PDI) as evaluation indicators. The physical and chemical properties, and preliminary stability of FNB-SMEDDS were evaluated. RESULTS The optimal prescription of FNB-SMEDDS was ethyl oleate (EO) 22.86% as oil phase, polyoxyethylene (40) hydrogenated castor oil (cremophor RH40) 51.07% as surfactant, diethylene glycol monoethyl ether (transcutol HP) 26.07% as co-surfactant. The obtained FNB-SMEDDS was uniform and transparent. The FNB-SMEDDS was self-emulsified in water with average particle size of (39.29±0.45) nm, PDI of (0.11±0.01), Zeta potential of (-7.7±0.9) mV, drug loading rate of 15 mg·g-1, encapsulation rate of (95.11±0.26)%, and emulsification time of (56.03±1.65) s. Stability experiments showed that after being stored at room temperature in the dark for 30 days, there was no significant change in its index components and appearance properties, indicating good stability. Compared with FNB API, FNB-SMEDDS significantly improved the in vitro dissolution of FNB. The cumulative release rates in water, pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution for 120 min were (97.68±0.61)%, (92.23±4.07)% and (93.65±2.25)%, respectively. CONCLUSION FNB-SMEDDS has good appearance, high emulsification efficiency. It can significantly improve in vitro dissolution of the drug, and is expected to improve the in vivo bioavailability of FNB.

fenofibrate  /  self-microemulsifying drug delivery system  /  pseudoternary phase diagram  /  central composite design-response surface methodology  /  quality evaluation  /  dissolution
吕江维, 姜京京, 陈威, 赵雪莹, 张文君, 曲有鹏. 非诺贝特自微乳给药系统的制备及质量评价. 中国药学杂志, 2024 , 59 (24) : 2343 -2353 . DOI: 10.11669/cpj.2024.24.007
Jiangwei LÜ, Jingjing JIANG, Wei CHEN, Xueying ZHAO, Wenjun ZHANG, Youpeng QU. Preparation and Evaluation of Fenofibrate Self-microemulsifying Drug Delivery System[J]. Chinese Pharmaceutical Journal, 2024 , 59 (24) : 2343 -2353 . DOI: 10.11669/cpj.2024.24.007
正文
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非诺贝特(fenofibrate,FNB)作为第三代氯贝丁酯类降血脂药,具有疗效显著、毒性和副作用较小、耐受性良好等优点,在临床上常用于高血脂的治疗[1-2]。但FNB属于生物药剂学分类系统(biopharmaceutics classification system,BCS)中的Ⅱ类难溶性药物[3],在水中的溶解度极低,不易于口服吸收,导致生物利用度较低,仅为30%[4],影响其临床疗效。因此,改善其水溶性和溶出速率是提高生物利用度的关键因素。
目前,国内外已采用微粉化技术、纳米结晶技术、固体分散技术、微粒分散体系等多种技术来增加FNB的溶解度和体外溶出[5-7]。但药物微粉化后的物理化学稳定性较差,容易重新聚集,易受水分、O2等因素的影响,且这种粗分散状态的药物粉末对生物利用度的提高比较有限;纳米结晶技术多采用机械研磨粉碎法,需要相应的生产设备,存在设备能耗高、易磨损、工艺复杂的缺点;固体分散体中药物的稳定性问题及开发成熟的工业化制备技术限制了该法的广泛应用;微粒分散体系中聚合物胶束相对分子质量大导致载药量较小,部分脂质体对药物包封率低,体内可能发生药物突释,部分纳米混悬液的稳定性较差。
与上述技术相比,自微乳给药系统(self-microemulsifying drug delivery system, SMEDDS) [8-9]是一种提高水难溶性药物溶解度的有效方法,它是由自然或人工合成的油相、表面活性剂和助表面活性剂构成的具有一定黏性的油性混合物,难溶性药物主要溶解于油相中。自微乳在水性介质中(37 ℃)可以通过温和搅拌或在胃肠消化运动下自发形成粒径在10~100 nm之间水包油型微乳液[10-12]。自微乳在胃肠道中自发形成微乳液,药物是以溶解状态存在的,有利于提高药物的体内生物利用度,是疏水性难溶性药物的理想载体[13],并且具有良好的生物相容性、稳定性和控释性[14]。处方中的脂质不仅能够增加药物的溶解度和溶出速率,还能避免药物被酶降解,脂质通过刺激产生脂蛋白和乳糜微粒增强淋巴药物转运,从而避免肝门静脉的首过效应,显著提高生物利用度[15]。在SMEEDS的处方筛选中,伪三元相图[16]是一种重要的辅助方法,它可以帮助快速简便地获得形成自微乳的区域范围,通常还需与预测效果更好的星点设计-效应面法[17-19]结合,既可以对最佳处方进行科学、精确地筛选,又可以克服实验精度低、预测性差的缺点。
基于此,本研究采用SMEDDS来提高难溶性药物FNB的溶出,利用伪三元相图法筛选SMEDDS处方及比例范围,并结合星点设计-效应面法优化FNB-SMEDDS自微乳的处方,并对FNB-SMEDDS的质量进行评价,为开发FNB新剂型,以期提高其体内生物利用度提供依据。
1 试剂与仪器
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1.1 试剂
FNB(纯度≥99%,批号:S17137)、花生油(分析纯,批号:S27176)、油酸乙酯(EO,分析纯,批号:S24222)、聚氧乙烯(40)氢化蓖麻油(Cremophor RH40,分析纯,批号:S25692)(上海源叶生物科技有限公司);二乙二醇单乙基醚(Transcutol HP,分析纯,批号:2020051132A)(广东翁江化学试剂有限公司);Tween 80(分析纯,批号:20190715)(天津市大茂化学试剂厂);甲醇、氢氧化钠、磷酸二氢钠、1,2-丙二醇、Tween 20、盐酸均为分析纯;PEG 400(上海阿拉丁生化科技股份有限公司)。
1.2 仪器
UV-7504型紫外可见分光光度计(天津奥特赛恩斯仪器有限公司);SHA-A型水浴恒温振荡器(江苏金坛市环宇科学仪器厂);FA2204B型电子天平(上海精科天美科学仪器有限公司);洁盟牌超声波清洗机(深圳市洁盟清洗设备有限公司);DGX-8053B型恒温鼓风干燥箱(上海福玛实验设备有限公司);DF-101S型集热式恒温加热磁力搅拌器(巩义市予华仪器有限责任公司);Litesizer 500型纳米激光粒度仪[安东帕(上海)商贸有限公司];TraceableTM实验室台式计时器[赛默飞世尔科技(中国)有限公司];Mix Max型涡旋振荡器(合肥艾本森科学仪器有限公司)。
2 方法与结果
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2.1 FNB含量测定
2.1.1 测定波长的选择
称取FNB对照品、处方内空白辅料,加甲醇溶解配制成10.00 μg·mL-1的FNB溶液,在200~400 nm的波长范围内进行紫外全波长扫描。实验结果发现,FNB在250 nm左右和287 nm处有较大紫外吸收,但各辅料在250 nm左右有明显吸收峰,影响较大,而287 nm无影响,确定FNB的测定波长为287 nm。
2.1.2 线性关系考察
精密称取FNB对照品10.0 mg,以甲醇为溶剂,配制100.00 μg·mL-1的储备液。精密量取FNB对照品储备液,配置成质量浓度2.0、8.0、10.0、16.0、18.0和20.0 μg·mL-1的溶液。在测定波长287 nm处测定吸光度(A)。以吸光度(A)为纵坐标,FNB溶液质量浓度(ρ)为横坐标,绘制标准曲线。标准曲线方程为A=0.048 8ρ+0.009 1,r=0.999 7,线性范围为2~20 μg·mL-1。
2.1.3 方法学考察实验
精确量取FNB对照品储备液,用甲醇定容,按“2.1.2”项下方法配制成不同浓度对照品溶液进行方法学考察。结果发现,此方法的专属性良好,日内、日间精密度相对标准偏差(RSD)均小于2.0% (n=3);回收率在99.34%~100.47%之间,RSD小于2.0% (n=3);24 h内稳定性良好,RSD值为1.02%,符合测定要求。
2.1.4 自微乳中药物含量测定
取适量FNB-SMEDDS,用甲醇定容,微孔滤膜过滤,取续滤液在紫外波长287 nm处测定吸光度(A),由标准曲线计算得到FNB的含量。
2.2 FNB-SMEDDS处方筛选
2.2.1 FNB在药用辅料中的溶解度测定
称取过量FNB原料药分别加入精密称取的1 g的EO、大豆油、花生油、Tween 20、Tween 80、聚氧乙烯(40)氢化蓖麻油(Cremophor RH40)、二乙二醇单乙基醚(Transcutol HP)、PEG 400和1,2-丙二醇中,密封,涡旋混匀,(37±1)℃恒温震荡72 h,达到平衡后,5 000 r·min-1离心5 min,取部分上清液,微孔滤膜过滤,取续滤液测定FNB质量浓度,得到FNB在不同油相、表面活性剂和助表面活性剂中的溶解度见图1。
FNB在各油相中的溶解度顺序为:EO>大豆油>花生油。FNB在EO中的溶解度比花生油、大豆油中的溶解度大,说明人工合成的油脂对难溶性药物的溶解效果优于天然油脂,所以选择EO作为油相。FNB在不同的表面活性剂中的溶解度顺序为:Tween 20>Tween 80>Cremophor RH40。Tween 20、Tween 80和Cremophor RH40对FNB的溶解能力差别不大,因此选择油相和表面活性剂的配伍实验继续进行表面活性剂的筛选。FNB在不同助表面活性剂中溶解度顺序为:Transcutol HP>PEG 400>1,2-丙二醇。FNB在Transcutol HP中的溶解度最好,所以选择Transcutol HP作为助表面活性剂。基于溶解度测定结果,初步确定EO为油相,Tween 20、Tween 80和Cremophor RH40为表面活性剂,Transcutol HP作为助表面活性剂进一步用于SMEDDS处方筛选。
2.2.2 油相和不同表面活性剂的配伍
通过配伍实验可以进一步确定SMEDDS中的油相和表面活性剂的相容性和乳化性能,将油相EO与表面活性剂(Tween 20、Tween 80和cremophor RH40)分别按1∶9、2∶8、3∶7、4∶6、5∶5、6∶4、7∶3的比例混合,磁力搅拌(温度37 ℃)混匀后,将蒸馏水添加到混合溶液中,以其外观和乳化时间作为评估油相与表面活性剂的相容性的指标。自微乳化的情况分为5个级别:A级:溶液呈澄清或泛蓝色乳光,乳化时间<1 min;B级:外观略浊,乳化时间<2 min;C级:呈亮白色不透明液体,乳化时间1~3 min;D级:色泽暗,呈灰白色,略带油状,乳化时间>3 min;E级:难以乳化,一直有油滴存在,乳化时间>3 min。
配伍实验结果见表1,在油相与不同表面活性剂配伍中,EO与Cremophor RH40和Tween 80配伍时所得的A和B等级结果相当。因此,继续采用伪三元相图法确定表面活性剂的种类。
2.2.3 伪三元相图法筛选SMEDDS处方及比例范围
采用伪三元相图,分别以油相EO、表面活性剂(Cremophor RH40和Tween 80)及助表面活性剂(Transcutol HP)作为三元相图的3个顶点,按照相图内各点比例配制空白SMEDDS,涡旋充分混匀为均一透明的溶液,然后加入100倍体积的蒸馏水中,搅拌均匀,形成一种清澈的或带有浅蓝色乳光的溶液,可称为微乳液。把能构成微乳液的点连在一起,它所覆盖的就是微乳区。结果见图2,灰色区域代表微乳区。通过对两个伪三元相图的微乳区的比较,发现当表面活性剂为Cremophor RH40时,形成的微乳区较大,所以确定Cremophor RH40为表面活性剂。从图2(A)可以进一步看出,当自微乳处方中油相含量为10%以下或者30%以上时,会形成粗糙的乳状物,不能形成澄清的微乳。在10%~30%的油相中,可乳化出均匀透明的微乳。所以在处方中,油相EO的用量限制在10%~30%,表面活性剂与助表面活性剂的质量比值(Km)定为0.5~4。伪三元相图是筛选自微乳处方的一种重要辅助方法,但它只能对处方中各组分的范围进行初步确定,进一步采用星点设计-效应面法,对初步筛选的自微乳处方进行优化。
2.3 星点设计-效应面法优化FNB-SMEDDS处方
2.3.1 星点设计(central-composite design,CCD)
根据配伍实验及伪三元相图,初步确定了处方组成及各成分的比例范围,采用CCD设计,以油相EO的百分含量(X1)、表面活性剂Cremophor RH40和助表面活性剂Transcutol HP的质量比Km(X2)为考察因素,以平衡溶解度(Y1)、粒径(Y2)、PDI(Y3)作为效应指标。采用Design Expert软件进行两因素五水平(±α、0、±1)的实验设计,具体因素水平表见表2。
2.3.2 模型拟合
按处方比例精密称取EO、Cremophor RH40、Transcutol HP,37 ℃磁力搅拌后加入过量FNB,密封,涡旋混匀,(37±1)℃恒温震荡72 h,达到平衡后,5 000 r·min-1离心5 min,取部分上清夜,微孔滤膜过滤,取续滤液按“2.1.4”项下方法测定FNB质量浓度,该上清液即为FNB-SMEDDS浓缩液。取FNB-SMEDDS浓缩液,加纯化水稀释适当的倍数,摇匀,移取适量上清液,采用激光粒度仪测定平均粒径及PDI。得到星点实验设计结果见表3,在此基础上,利用多元线性回归和二次多项式回归方程拟合了各参数与效应值的关系。以拟合度r2和置信度P为判据,分别确定各效应指标的最优拟合公式。
溶解度:Y1=106.81+1.89X1-11.50X2-1.01X1X2-4.41 X 1 2-6.81 X 2 2(r2=0.900 4,P=0.002 1)
粒径:Y2=35.93+2.40X1-3.41X2-4.85X1X2+7.10 X 1 2+5.30 X 2 2(r2=0.903 1,P=0.002 0)
PDI:Y3=14.12-4.91X1+1.03X2-1.43X1X2+0.99 X 1 2+3.41 X 2 2(r2=0.921 9,P=0.000 9)
由上述结果可知,溶解度(Y1)、粒径(Y2)、PDI(Y3)对应的二次多项式非线性拟合方程具有较高的相关系数(r2>0.9),说明采用的二次多项式模型拟合效果较好;其中,Y1、Y2、Y3的显著性水平P<0.01,结果具有统计学意义。
2.3.3 效应面、等高线分析及处方优化
采用回归方程拟合得到的最优分析模式,并绘制了相应的效应面图和等高线图(图3)。从图3可以看出,在Km值一定的情况下,随油相百分含量的增加,溶解度先增大后降低,粒径先减小后增大,多分散系数(PDI)逐渐降低;在油相百分含量一定时,溶解度随Km值的升高先增加后降低,粒径和PDI先减小后增大。以粒径及PDI最小,平衡溶解度最大为限制条件进行处方优化,得到了制备FNB-SMEDDS的最优条件为Km=1.96,油相的百分含量为22.86%。即FNB-SMEDDS最优处方为22.86%EO,51.07%Cremophor RH40,26.06%Transcutol HP。
2.3.4 最优处方验证
为检验该模型的可信性,将SMEDDS的最优处方平行制备3组,对平衡溶解度、平均粒径及PDI进行了测定,比较实测值与预测值之间差异,按照公式1计算相对误差。
相对误差(%)= 预 测 值 - 实 测 值 预 测 值×100%
实验结果见表4,所预测的各项指标与实际测量值相差不大,相对误差在5%以内,该模型具有较高的预测精度和可靠性。
2.3.5 载药量的确定
根据“2.3.3”项下筛选得到的最优处方,分别按含药量10、15、20、40、60、80、100和105 mg·g-1加入FNB,将自微乳浓缩液经水自乳化后的微乳液放置过夜观察。结果发现在药物加入量超过15 mg·g-1的情况下,微乳液的稳定性随FNB加入量的增加而下降,放置后会产生沉淀。可能是在过量载药条件下,自乳化后药物超过了微乳液乳滴能承载的药物量,部分药物会溶解于由乳化剂构成的胶团中,但其增溶能力有限,未溶解的药物会析出沉淀[20]。当自微乳中FNB的加入量为15 mg·g-1时,长期放置于室温下,微乳液中不产生沉淀。由于自微乳通过口服的方式进入人体,与消化道液接触形成微乳液,为了避免FNB在消化道中沉积,SMEDDS中FNB的载药量确定为15 mg·g-1。
2.3.6 FNB-SMEDDS的制备
精密称取EO 2.286 g、Cremophor RH40 5.107 g、Transcutol HP 2.606 g、FNB 0.150 g置于西林瓶中,37 ℃下磁力搅拌,得到FNB-SMEDDS浓缩液。向FNB-SMEDDS浓缩液中加入适量体积水,37 ℃磁力搅拌至呈蓝色乳光状态,得到FNB-SMEDDS微乳液。制备工艺流程示意图见图4。
2.4 FNB-SEMDDS的质量评价
2.4.1 外观评价
按照“2.3.6”项下方法制备FNB-SMEDDS浓缩液,分别用蒸馏水、pH 1.2盐酸溶液、pH 6.8磷酸盐缓冲液稀释100倍,逐滴加入并搅拌至完全形成微乳液,进行观察,结果见图5。由图5可见,常温下,FNB-SMEDDS浓缩液为带有浅黄色的澄清液体,流动性良好,而稀释后在不同的体内pH模拟体条件下,均能够完全乳化。
2.4.2 微乳类型鉴别
将FNB-SMEDDS浓缩液用蒸馏水稀释,逐滴加入并搅拌至完全形成微乳液。将苏丹红和亚甲蓝分别添加到微乳液中,观察其在微乳液中的扩散速率,以确定微乳液的种类。鉴别结果见图6,水溶性染料(亚甲蓝)快速地在微乳液中扩散,而油溶性染料(苏丹红)在沉降时不会发生扩散,说明FNB-SMEDDS微乳液是水包油型(O/W)。
2.4.3 粒径分布及PDI
将FNB-SMEDDS浓缩液分别用蒸馏水、pH 1.2盐酸溶液、pH 6.8磷酸盐缓冲液稀释100倍,逐滴加入并搅拌,直至完全形成自微乳。采用纳米激光粒度仪测定平均粒径及PDI。
在不同介质中,FNB-SMEDDS微乳液的粒径分布都很集中,粒径在39 nm左右,PDI在0.11左右,粒径大小均一,见图7。在不同的pH值条件下,FNB-SMEDDS微乳液的粒径与PDI之间的差异很小,表明自乳化性能良好。
2.4.4 Zeta电位
将FNB-SMEDDS浓缩液用蒸馏水稀释100倍,逐滴加入并搅拌至完全形成微乳液,采用纳米激光粒度仪测定Zeta电位。结果见图8,FNB-SMEDDS的Zeta电位为(-7.7±0.9) mV,电位值分布较为集中,偏离很小。
2.4.5 乳化时间的测定
将FNB-SMEDDS浓缩液用蒸馏水稀释,逐滴加入并搅拌。从微乳液与蒸馏水接触时开始,到微乳完全乳化,形成一种清澈的、透明的乳液时,停止计时。FNB-SMEDDS与水接触至完全分散形成澄清透明的微乳所需的乳化时间为(56.03±1.65) s,乳化迅速且乳化效率高。
2.4.6 包封率测定
称取适量FNB-SMEDDS浓缩液,经甲醇稀释后测定自微乳中FNB的含量,记为W1。另取适量FNB-SMEDDS浓缩液,按1∶100比例加入蒸馏水进行稀释,形成FNB-SMEDDS微乳液,再10 000 r·min-1离心10 min,将未包封的游离药物离心沉降至底层,取上清液经甲醇稀释后测定FNB的含量,记为W2。按照公式2计算FNB-SMEDDS的包封率。
包封率(%)= W 2 W 1×100%
测得自微乳对FNB的包封率为(95.11±0.26)%,较高的包封率对于维持FNB-SMEDDS的稳定性发挥了重要的作用,能够使制剂经口服进入体内避免出现药物沉淀的现象。
2.4.7 初步稳定性考察
离心及稀释稳定性:将适量FNB-SMEDDS置于离心管中,分别在3 000 r·min-1的转速下离心0.5 h、在10 000 r·min-1的转速下离心15 min。观察自微乳中的药物是否沉淀,以确定自微乳的稳定性。
向3份等体积的FNB-SMEDDS中分别加入不同体积(100、50、10倍)的蒸馏水,均匀混合后,在室温下放置过夜,观察自微乳的稀释稳定性。
结果发现不同转速离心后FNB-SMEDDS中没有药物沉淀,说明离心对自微乳的稳定性没有影响。用不同比例的蒸馏水稀释后,微乳液没有发生分层、絮凝、沉淀等现象,说明稀释比不影响自微乳的稳定性。
不同pH条件下稳定性:将FNB-SMEDDS浓缩液,分别用蒸馏水和pH 1.2、4.5、6.8、10.0的溶液稀释100倍,搅拌直到能够形成清澈、透明的微乳液,在室温下放置1晚,观察pH值对自微乳稳定性的影响。
从图9可以看出,FNB-SMEDDS微乳液经过不同溶液稀释后,放置1晚依然清澈透明,没有析出,说明FNB-SMEDDS在各种pH值下都能保持较好的稳定性。
室温光照稳定性:由于时间有限,故未对样品进行长期稳定性测试,仅对室温条件下短期(30 d)样品的光照稳定性进行了测试。平行制备3批FNB-SMEDDS,将其于室温(25 ℃)条件下(避光和不避光)保存,分别于10、20、30 d时,用蒸馏水将0.1 g样品稀释到20 g,然后轻轻搅拌。对所制备的微乳液进行观察,并检测其离心后有无分层现象,同时测定平均粒径和FNB的含量。
研究发现,3批样品在室温光照条件下,10、20和30 d的FNB含量为(12.99±0.15)(12.34±0.34)和(10.98±0.30)mg·g-1,含量逐渐降低;10、20和30 d的粒径分别为(45.99±2.70) (61.08±2.89)和(79.52±0.85) nm,粒径有增大的趋势。而且观察到放置后乳液有轻微的沉淀,离心后微乳液不是特别稳定。3批样品避光条件,10、20和30 d FNB含量为(14.15±0.10) (13.48±0.15)和(12.78±0.23) mg·g-1,含量略有降低;10、20和30 d的粒径为(39.05±0.39) (39.21±0.36)和(39.44±0.23) nm,粒径没有显著变化,放置后仍然能保持原有的透明状态,离心后也没有出现分层、絮凝等现象。FNB-SMEDDS中的油相为EO,是淡黄色油状液体,属于高级脂肪酸醇酯,光照不稳定,导致FNB-SMEDDS在光照条件下出现了分层及药物沉淀析出,说明FNB-SMEDDS制剂应当室温避光保存。
热力学稳定性:平行制备3批FNB-SMEDDS,将其置于4 ℃冷藏24 h后,立即取出,并在40 ℃下贮存24 h。以上的循环重复4次。每一次储存条件转换时,取样品0.1 g用蒸馏水稀释到20 g,然后轻轻搅拌。对所制备的微乳液进行观察,并检测其离心后有无分层现象,同时测定平均粒径和FNB的含量。
研究发现,每次循环后的3批样品,用蒸馏水稀释稍加搅拌,便可自然生成均匀透明的微乳液,粒径和FNB含量基本没有变化,离心和稀释后也没有分层现象,说明所制得的FNB-SMEDDS的热力学稳定性好,能在不同温度条件下保持稳定。
2.4.8 体外溶出度测定
称取FNB原料药和FNB-SMEDDS适量,按照《中国药典》2020年版四部通则0931溶出度与释放度测定法[第二法(桨法)],分别配制溶出介质为5 mg·mL-1十二烷基硫酸钠(SDS)水溶液及 5 mg·mL-1的pH 1.2的盐酸溶液和pH 6.8的磷酸盐缓冲溶液900 mL,转速50 r·min-1,温度(37±0.5)℃,依法操作,分别于不同时间点取5 mL样品,同时补充同温溶出介质5 mL,样品经6 000 r·min-1离心10 min,取上清液(含FNB-SMEDDS微乳液)用溶出介质稀释一定倍数,采用紫外-可见分光光度法测定FNB浓度,按公式3计算累积释放度,比较FNB原料药和FNB-SMEDDS的溶出规律,结果见图10。
Qn= V 0 ρ n + V ∑ i = 1 n = 1 ρ i M×100%
式中,V0为900 mL的各种溶出介质;V为每次取样的体积为5 mL;ρn为不同时间点的取样质量浓度(μg·mL-1);ρi为第i次所取样品的质量浓度(μg·mL-1);M为溶出介质中药物的总质量(μg)。
由图10可知,FNB-SMEDDS在不同溶出介质中的溶出度并无显著差异,20 min左右均可以接近溶出平台,在水、pH 1.2盐酸溶液和pH 6.8缓冲液中120 min的累积释放率分别为(97.68±0.61)%、(92.23±4.07)%和(93.65±2.25)%;而FNB原料药最终的溶出度仅达到20%~30%。表明将FNB制备为自微乳制剂可显著提高溶出,进而有望改善其在体内的吸收程度和生物利用度。
3 讨论
收起
SMEDDS处方中所选用的辅料需要对FNB有较高的溶解能力,并尽量减少辅料的种类及用量。油相是SMEDDS处方中最重要的组分之一,FNB是脂溶性药物,主要溶解于油相中,研究发现其在脂肪酸酯类油相EO中的溶解度高于天然植物油大豆油和花生油。EO为无色至淡黄色油状液体,流动性好,黏度较小,为3.9 mPa·s,且易被身体组织快速吸收,其溶解性和成乳能力均比植物油好[21]。因此油相确定为EO。在表面活性剂筛选过程中,除了考虑其对FNB的溶解能力外,更重要的是表面活性剂与油相形成微乳的能力。当油相和表面活性剂具有较好的配伍效果时,能够提高自微乳的稳定性及乳化效果;否则可能稳定性较差,易产生絮凝及团聚等现象。根据Pouton提出的脂质制剂分类系统(lipid formulation classification system,LFCS)[22-23],O/W型自微乳属于ⅢB型,一般多采用的亲水亲油平衡值(hydrophile lipophile balance,HLB)≥12的非离子型表面活性剂,该类型的乳化剂有利于自微乳遇水性介质迅速分散形成较小粒径的微乳液滴,能够起到改善药物吸收,增加生物利用度效果。本研究通过配伍实验并结合伪三元相图,发现表面活性剂为Cremophor RH40时,与油相EO的配伍较好且形成的微乳区较大。这是因为Cremophor RH40属于非离子表面活性剂,HLB值约14~16[24],亲水性较好,易形成O/W稳定的微乳。与其他表面活性剂相比,尽管其对FNB的溶解度略低,但由于乳化效果好,确定Cremophor RH40为表面活性剂。对于助表面活性剂的选择主要考虑FNB在Transcutol HP中的溶解度显著高于其他两种,确定Transcutol HP为助乳化剂。
根据伪三元相图确定了油相EO的用量限制在10%~30%,表面活性剂Cremophor RH40与助表面活性剂Transcutol HP的质量比值(Km)为0.5~4。伪三元相图是研究微乳形成区域的基础工具,它简单方便快速,是筛选自微乳处方的一种重要辅助方法,但它只能对处方中各组分的使用范围初步确定,而处方中各辅料的最佳比例,需要通过其他方法来进行优化。本研究采用效应面法中的CCD设计进一步对处方进行优化,该方法可以用于线性及非线性模型,具有较高的优化效率和准确性。在CCD设计中,考察因素的选择和效应指标的设定对于制剂处方的优化起到决定性作用。考察因素不宜过多,否则实验组数会增加而且拟合函数会更复杂,实验优化的目的是确定对效应有显著影响的因素,所以选择与自微乳处方最相关的油相EO的百分含量、表面活性剂与助表面活性剂比例(Km)为考察因素。在效应指标的选择上,要以载药处方为最终目标,选择药物溶解度、粒径及PDI作为评价指标。这主要是因为药物溶解度的大小直接影响到自微乳中的载药量及临床应用的剂量,溶解度越大,越易满足临床需要;而粒径及分布特性影响体系的稳定性和在体内的吸收,粒径越小,分布越均匀集中,油水界面积越大,稳定性、吸收越好,生物利用度越高。
自微乳乳化后的粒径与药物释放密切相关。本研究中FNB-SMEDDS在水中自乳化后粒径很小且分布均匀,平均粒径(39.29±0.45) nm,PDI为(0.11±0.01)<0.3。与FNB原料药相比,FNB-SMEDDS在不同介质中120 min的累积溶出度均在90%以上,而FNB原料药仅达到20%~30%,FNB-SMEDDS显著提高了FNB的体外溶出度。这与较小的粒径可以提供较大的界面面积,有利于药物的体外溶出有直接关系。本研究制备的FNB-SMEDDS的乳化粒径小于文献[25]报道的同类FNB液体微乳的粒径[(124.36±2.49) nm,PDI(0.10±0.02)]。
SMEDDS口服给药后首先经过低pH的胃液,随后转运到稍高pH的肠液,在肠液环境下乳化成乳剂,pH的变化会影响自微乳的稳定[26]。因此本研究对FNB-SMEDDS不同pH条件下(中性蒸馏水及pH 1.2盐酸溶液、pH 4.5磷酸盐缓冲溶液、pH 6.8磷酸盐缓冲溶液、pH 10的磷酸盐缓冲溶液的稳定性进行了研究,发现各种pH值下都能保持较好的稳定性。
Zeta电位通常是用于评价SMEDDS稳定性的重要指标,一般认为Zeta电位的绝对值大于30 mV,体系相对稳定[24]。尽管FNB-SMEDDS的Zeta电位为(-7.7±0.9) mV,绝对值不是很大,但其他初步稳定性考察均表明其稳定性良好,说明本研究制备的FNB-SMEDDS的物理稳定性受电位的影响较小,自微乳可能是通过稳定界面膜的机制增加了体系的稳定性,阻止乳滴间的聚集及絮凝现象的产生。
本研究制备的FNB-SMEDDS外观均一,乳化效率高,能显著提高药物的体外溶出,有望增加难溶性药物FNB的体内吸收,改善生物利用度,为FNB新剂型的开发与应用提供了理论基础,具有良好的发展前景。
基金
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  • 国家重点研发计划项目(MB20160087)
  • 2019年哈尔滨商业大学青年人才专项计划项目(2019CX12)
文献
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参考文献 引证文献
排序方式：
[1]
VAN BILSEN M, VAN NIEUWENHOVEN F A. PPARs as therapeutic targets in cardiovascular disease[J]. Expert Opin Ther Targets, 2010, 14(10):1029-1045.
[2]
SAHA M, DHIMAN S, GUPTA G D, et al. An investigative review for pharmaceutical analysis of fenofibrate[J]. J Chromatogr Sci, 2023, 61(5):494-504.
[3]
AMIDON G L, LENNERNAS H, SHAH V P, et al. A theoretical basis for a biopharmaceutic drug classification: the correlation of in-vitro drug product dissolution and in-vivo bioavailability[J]. Pharm Res, 1995, 12(3):413-420.
[4]
JIA Z, LIN P, XIANG Y, et al. A novel nanomatrix system consisted of colloidal silica and pH-sensitive polymethylacrylate improves the oral bioavailability of fenofibrate[J]. Eur J Pharm Biopharm, 2011, 79(1):126-134.
[5]
FENG Q Q, ZHANG T Y, LIU R, et al. Research progress of fenofibrate preparation[J]. J Pharm Res(药学研究), 2023, 42(3):199-203.
[6]
LI F, FENG L L, YAN C. Research progress of fenofi brate formulation[J]. World Clin Drugs(世界临床药物), 2011, 32 (9): 552-557.
[7]
KUMAR R. Solubility and bioavailability of fenofibrate nanoformulations[J]. Chemistryselect, 2020, 5(4):1478-1490.
[8]
KARWAL R, GARG T, RATH G, et al. Current trends in self-emulsifying drug-delivery systems (SEDDSs) to enhance the bioavailability of poorly water-soluble drugs[J]. Crit Rev Ther Drug Carrier Sys, 2016, 33(1):1-39.
[9]
SILBERSTEIN S, SPIERINGS E L H, KUNKEL T. Celecoxib oral solution and the benefits of self-microemulsifying drug delivery systems (SMEDDS) technology: a narrative review[J]. Pain Therapy, 2023, 12(5):1109-1119.
[10]
SERMKAEW N, KETJINDA W, BOONME P, et al. Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of andrographis paniculata[J]. Eur J Pharm Sci, 2013, 50(3-4):459-466.
[11]
MAHMOUD D B, SHUKR M H, BENDAS E R. In vitro and in vivo evaluation of self-nanoemulsifying drug delivery systems of cilostazol for oral and parenteral administration[J]. Int J Pharm, 2014, 476(1-2):60-69.
[12]
JIN K, LV J, BEN Y, et al. Research progress of solid self-microemulsion drug delivery system[J]. J Pharm Res(药学研究), 2023, 42(2):126-129,144.
[13]
PATEL A R, VAVIA P R. Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate[J]. AAPS J, 2007, 9(3):E344-E352.
[14]
LIU C S, CHEN L, HU Y N, et al. Self-microemulsifying drug delivery system for improved oral delivery and hypnotic efficacy of ferulic acid[J]. Int J Nanomed, 2020, 15:2059-2070.
[15]
ZHANG N, ZHOU H B, QUAN D Q. Mechanism and application of self-microemulsion drug release system to improve drug bioavailability[J]. Chin Med Biotechnol(中国医药生物技术), 2009, 4(1):47-50.
[16]
CHEN G, QU H, XIE M, et al. Research on prescription of eczema nanoemulsion based on pseudo ternary phase diagram method[J]. Chin Pharm J(中国药学杂志), 2023, 58(12):1110-1116.
[17]
FANG Z, HUANG W, QI J, et al. Progress on application of central composite design-response surface methodology in optimization of preparations in China[J]. Acta Pharm Sin(药学学报), 2021, 56(1):169-177.
[18]
XU Z, ZHANG X, SU S, et al. Compatibility optimization and anti-inflammatory effects of salvianolic acid B and tanshinone ⅡA in protecting renal cells injured by high glucose based on star point design-response surface methodology[J]. Chin Pharm J(中国药学杂志), 2023, 58(11):987-996.
[19]
ZHANG K, FU H, WANG Y, et al. Micro-porous osmotic pump and elementary osmotic pump controlled-release tablets of zalcitabine[J]. Chin Pharm J(中国药学杂志), 2023, 58(5):435-446.
[20]
ZHANG R, YANG B, LIAO M, et al. Preparation and evaluation of dihydroartemisinin self-microemulsion drug delivery system[J]. Chin Tradit Herb Drugs(中草药), 2021, 52(5):1291-1302.
[21]
LU X, HE L, CHEN J, et al. Preparation and in vitro dissolution evaluation of tanshinone ⅡA for oral self-microemulsion[J]. Chin Tradit Herb Drugs(中草药), 2014, 45(22):3256-3265.
[22]
POUTON C W. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems[J]. Eur J Pharm Sci, 2000, 11(S2):S93-S98.
[23]
POUTON C W. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system[J]. Eur J Pharm Sci, 2006, 29(3-4):278-287.
[24]
HSIEH C M, YANG T L, PUTRI A D, et al. Application of design of experiments in the development of self-microemulsifying drug delivery systems[J]. Pharmaceuticals, 2023, 16(2):283.
[25]
QUAN G, WU Q, ZHANG X, et al. Enhancing in vitro dissolution and in vivo bioavailability of fenofibrate by solid self-emulsifying matrix combined with SBA-15 mesoporous silica[J]. Colloids Surfaces B-Biointerfaces, 2016, 141:476-482.
[26]
LI W, SUN J, WANG R. Overview and research progress of self-emulsifying drug delivery systems[J]. J China Pharm(中国药房), 2014, 25(37):3528-3532.
2024年第59卷第24期
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doi: 10.11669/cpj.2024.24.007
  • 接收时间：2024-02-28
  • 首发时间：2025-11-13
  • 出版时间：2024-12-22
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  • 收稿日期：2024-02-28
基金
国家重点研发计划项目(MB20160087)
2019年哈尔滨商业大学青年人才专项计划项目(2019CX12)
作者信息
    1 哈尔滨商业大学药学院, 哈尔滨 150076
    2 哈尔滨工业大学生命科学与技术学院, 哈尔滨 150080

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* 张文君,女,博士,教授,硕士生导师 研究方向:新型药物传输系统 Tel:(0451)84838207
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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