[生物医药论文精品a]氯霉素耳丸的工艺质量研究

氯霉素耳丸的工艺质量研究A1A21,2A3A0A4A5A7A6A8A9A10A11A12A13A14A15A16A17A18A19A20A16A21A13A14A22A23A23A23A22A22A24A25A26A27A28A29A30A31A32A33A34A35A36A37A38A39A22A23A23A23A22A22A24A40A41A40A41A40A41A42A42A43A44A42A45A46A47A48A49A50A51A52A53A54A55A56A57A58A59A47A48A49A50A51A60A61A62A63A64A65A66A51A67A68A69A52A70A71A72A73A74A75A76A77A78A62A79A80A81A51A70A71A52A82A83A84A49A85A86A87A88A57A89A90A91A92A93A52A94A95A96A97A98A55A56A99A100A74A101A102A42A103A103A104A104A105A47A48A49A50A51A52A64A65A79A80A84A49A106A107A108A109A70A110A111A57A112A113A71A52A114A115A116A109A70A117A118A119A120A121A122A71A123A124A125A109A70A126A127A128A129A64A65A130A131A132A133A134A135A136A137A138A125A139A52A120A121A126A127A140A129A141A142A63A143A57A144A126A145A79A80A81A51A146A147A143A132A133A148A135A149A120A51A67A52A95A150A151A152A153A77A128A129A154A155A156A143A66A149A120A154A155A141A143A66A157A158A81A53A159A160A66A149A161A81A162A163A164A165A101A166A101A166A42A78A62A55A56A167A168A98A94A95A96A97A169A147A126A127A58A59A47A48A49A50A51A64A65A98A51A67A68A69A52A70A71A72A73A165A170A171A172A171A172A171A172A42A42A47A48A49A132A81A51A132A64A65A132A51A67A173A174A175A176A177A175A176A178A179A180A181A181A180A182A183A184A185A186A183A184A185A186A178A187STUDYONTHETECHNOLOGYANDQUALITYOFCHLORAMPHENICOLEARPILLSCHENBIAOA188WANGJIANHUAA188XIAOQIQIA189BIOENGINEERINGCOLLEGEOFCHONGQINGUNIVERSITY,CHONGQING,400044A190SOUTHWESTPHARMACEUTICALSCO,LTD,CHONGQING,400038ABSTRACTOBJECTIVERESEARCHPREPARATIONPROCESSOFCHLORAMPHENICOLEARPILLS,ANDSOLVETHEQUALITYPROBLEMSOFADHESIONANDTHESMALLERWEIGHTOFCHLORAMPHENICOLEARPILLSINPRODUCTIONPROCESSMETHODINMOREFACTORSTESTOFAFFECTINGTHEQUALITY,ANDSELECTTHEBESTPRESCRIPTIONDESIGNANDPROCESSPARAMETERSRESULT1THEMAININFLUENCINGADHESIONFACTORSOFCHLORAMPHENICOLEARPILLISTHECOMPOSITIONOFTHEMATRIX,ACERTAINAMOUNTOFPEGRATIOOFMATRIXORTOASMALLHYDROPHOBICMATRIXCANREDUCEADHESION2SURFACTANTSCANREDUCETHEEXTENTOFADHESIONS,BUTMAYAFFECTTHEROUNDNESSANDUNIFORMITYOFPILLS3THEFOURWAYSOFINCREASETHEPILLWEIGHTLOWERSOLUTIONTEMPERATURE,INCREASEDSOLUTIONVISCOSITY,REDUCEDDROPFROMTHESYSTEM,INCREASINGTHEEMITTERDIAMETERCONCLUSIONBYPRESCRIPTIONPROCESSOPTIMIZATIONANDDESIGNADJUSTMENTCANBESOLVEDTHEQUALITYPROBLEMSOFCHLORAMPHENICOLEARPILLADHESIONANDSMALLERWEIGHTPILLSKEYWORDSCHLORAMPHENICOLA191PILLSA191ADHESIONA191PILLWEIGHT滴丸剂是我国老一代药剂学家在60年代初，根据国外冶金工业滴制法工艺的启迪开发出来的为我国特有的独特药物剂型1。它是药物与固体基质加热熔融成溶液、混悬液或乳状液，再滴入不相溶的冷凝剂中，由于界面张力作用使液滴收缩并冷凝成A192A193A194A195A196A197A198A199A200A201A202A203A204A205A206A207A202A208A209A210A211A212A213A214A215A216A217A218A219A220A221A222A202A215A223A224A225A226A227A228A229A230A231A232A233A234A198A199A235A196A235A236A236A233A196A235A202A237A199A238A239A240A231A241A242A243A244A198A244A235A245A195A234A244A246A242A247A238固态球形的制剂。尽管它存在载药量较小、易老化等缺点，但作为一种基于固体分散技术的制剂，它具有速效、缓释、工艺简单、可腔道（耳、鼻、口腔等）给药等显著优点，广泛用于中药制剂和部分化学药制剂的研发领域2。氯霉G13044耳丸是用于G8847G11115中耳G9826等耳G1881腔道G5875G7591的滴丸，可G1209G4570耳丸G3634入耳G1881G4628部G19786G2533给药，G1032G5214效G7536G19762G5132G3921，是基于我G1856G2508固体分散技术制G17908G5191G2500G991开发的具有G14270G1039G11705G16794G1147G7447的剂型。在G4466G19481G10995G1147中，由于基质G13870G1069G1120G18267（PEG）G6221G19400不G12295G4462，G17908成滴丸G12908G17842、丸G18337G1571小等质量G19394G20076，G19668G16213G17839G15904工艺研G12362，G16311G1927G1147G2709质量G19394G20076G2530G1427于G6221量G16280G8181G990G5078。1材料与仪器氯霉G13044（G16211G2347G2524成G13941G1233有G19492G1856G2508，G6221G2507G726061208）G727G13870G1069G1120G182676000（PEG6000，G2283G1152G9035G9108G12946G13466化工G2390，G6221G2507G726061017）G727G13870G1069G1120G1826710000（PEG10000，广G1008G8745G3848G16211G19483化工G2390，G6221G2507G726061017）G727G13870G4677G7804G18267G1824380（G2532G921380，G2347G1152G4053G4584化工有G19492G1856G2508）G727G11840G14038G18252（G2347G1152G1908G2338化学G1856G2508）G727G11014基G11801G8845100（G2283G1152G5078G2319药G1856G2508）LB2DG4861G16311G7114G19492G8991G4462G1214（G990G9035G21656G9035药G7828G1214G3132G2390，G12591G13605G4392G54640425MM）G727单G3848滴丸G7438（G14270制）G727SDWJ481型G1852G14270G2172G4466G5527滴丸G7438（G2283G1152G19007G14334G12255G12197技发G4649有G19492G1856G2508）G727AGILENT1100G20652效液相G14406G16901G1214（G13666国AGILENTG1856G2508）2方法与结果G21G17G20制G3803工艺G3G21G17G20G17G20氯霉G13044耳丸的制G3803G3小试G726称取适量氯霉G13044和G13870G1069G1120G18267（PEG）（比例为G20G726G21），水浴加热融化至澄清溶液，作为料液，保G921380CG3803用G727用G1881G5464为3G17G21MM（外G54645G170MM）的滴G3848G17839G15904滴制，滴速（30滴/MIN）G727冷却柱G9213度G205C，冷却柱长G2000CM，滴距G200CM。G3如为车G19400中试G10995G1147，采用G1852G14270G2172G4466G5527滴丸G7438，工艺参数参考小试结G7536G17839G15904G12255序化设G4462，冷凝液循环G4466现丸G8845G14270G2172分离，滴制速度（G214滴/S）。G3G21G17G20G17G21G3在G9213度G208G215C的环境G991冷却48H，除去G11801G8845，G12591出G2524格粒G5464的滴丸，包装。G3G21G17G21G3质量G8991G4462A248A249A250G3G21G17G21G17G20G3溶散G7114G19492G8991G4462G3G3按照氯霉G13044耳丸质量标准G7828查，溶散G7114G19492为G2000MIN。G3G21G17G21G17G21G3圆整度G8991G4462G3G3参考微丸圆整度的G8991G4462方法A248A251A250，ARDA252A253A254/DA252A255A5,即小丸的最长直G5464（DA252A253A254）与最短直G5464（DA252A255A5）的比值，比值越小，圆整度越G3921，一般ARG20G17G21。G3G21G173G3基质的初步选择G3G3G3G3G13870G1069G1120G18267不同G13870G2524度类型对滴丸成型有不同的影响结G7536，选用不同基质和基质比例G17839G15904G4466验，考察滴丸的成型、G11840度、黏结情况,结G7536见表G20。G3A37A11A38A0A1A2A3A4A6A7A8A9A10A12A13A37G3A3A4A1A2A9A6A47A14A53A15A47A14A55A16A57A17A10A48A18A11A19A10A20A60A48A21A24A62A22A23A65A25A19A19A19A9A6A26A67A68A9A53A27A57A70A38A28A29A30A74A55A16A75A31A57A67A77A31A17A70A78A12A32A48A80A33A34A35A62A22A23A65A84A19A19A19A9A6A36A16A39A40A70A68A9A41A42A55A16A43A44A75A31A57A67A77A31A17A70A78A12A80A45A34A35A62A22A23A65A11A19A19A19A19A9A6A46A49A67A9A50A51A96A52A54A56A55A16A43A44A100A31A17A67A101A58A17A70A78A12A25A59A34A35A62A22A23A65A25A19A19A19A103A62A22A23A84A19A19A19A18A11A103A11A24A9A6A36A16A61A26A67A68A9A29A30A46A63A51A64A66A55A16A100A31A17A67A101A58A17A70A78A12A25A80A34A35A62A22A23A65A25A19A19A19A103A62A22A23A11A19A19A19A19A18A11A103A11A24A9A6A36A16A39A40A67A68A9A29A30A63A55A16A46A63A100A31A17A70A108A69A78A12A25A33A34A35A62A22A23A65A84A19A19A19A103A62A22A23A11A19A19A19A18A11A103A11A24A9A6A36A16A61A49A67A68A9A29A30A63A55A16A63A100A31A17A67A110A16A78A12A111A19A34A35氯霉G13044为难溶性药物，一般选用水溶性基质作为分散介质。PEG4000作为基质，滴丸的G11840度、流G2172性、耐热性差，可用PEG6000来调整，甚至可G1209用PEGG200000来部分调整，即不同比例的PEG复G2524基质可G1209有效G16311G1927滴丸G11840度、黏结、流G2172性等存在的G19394G20076。G3G21G174G3滴制G9213度的选择G3G3G3G3G13870G1069G1120G18267类受热G9213度过G20652会出现G14406泽加深不易凝固，所G1209选择G9213度和加热方式G19762G5132G18337G16213G727G4466验选用65C90C的G9213度范围考察滴丸滴出状态和丸G18337情况，结G7536见表G21。G3A37A59A9A6A71A16A8A72A73A12A13A9A6A71A16A115CA100A76A16A9A79A17A81A10A48A84A111A65A9A38A79A65A119A19A11A82A84A111A46A49A111A11A34A35A119A111A11A82A11A11A49A36A25A45A34A35A33A19A11A82A19A84A28A9A79A25A84A34A35A33A111A11A82A80A111A120A26A25A19A34A35滴制G9213度影响丸的圆整度和滴出状态。料G9213过底，溶液黏度大，不易滴出，且易出现拖尾，圆整度差G727料G9213过G20652，溶液黏度小，滴速太快，使滴丸表面皱折严G18337，圆整度降低。根据G4466验结G7536，选择7580G3C范围G9213度较G3921。G3G21G175G3冷凝剂的选择G3G3G3G3用PEG6000G726PEGG20000G20G726G20混G2524基质滴制耳丸，从G11014基G11801G8845（G12908G12276度G20000，G2100，G2000）、液体G11719G15605中选择G2524适的冷凝剂。G1209滴丸G991降速度、圆整度为考察G6363标，结G7536见表3。G3A37A80A121A83A68A85A86A72A73A12A13A121A83A68A125A87A36A16A100A76A16A127A3A88A89A11A19A19A19A130A49A11A82A111A84A127A3A88A89A59A19A19A46A49A11A82A11A59A127A3A88A89A11A19A19A39A40A11A82A19A111A68A90A91A92A26A11A82A80A111冷凝液的黏度和表面张力可影响滴丸的成型和圆整度。冷凝液G14521与药液的相对G4506度差大，G2029液滴G991降速度快，受冷凝液G9026力影响大，G18337力与G9026力的作用结G7536使滴丸G2588G6165球形。G11014基G11801G8845比G18337G13434为0G1797，与药液比G18337差小，可G1955小黏G9394力，G2045于滴丸成型，从表中结G7536G11487，G11014基G11801G8845G2000最G1351。G3G3G21G176G3药物与基质G2462G18209比的研G12362G3G3G3G3设G16757药物与基质G20G726G20G175，G20G726G21，G20G726G21G175G989种比例，并选择加入G11840G14038G18252、G2532G921380G17839G15904G4466验，考察黏结情况和丸G18337G6363标，结G7536见表4、表5。G3A37A25A38A0A3A4A1A2A93A94A95A1A37A93A94A134A97A98A103A3A4A55A99A102A140A71A65A33A19A11A11A103A11A82A111A65A65A59A11A103A11A82A111A80A104A65A80A11A103A11A82A111A80A104A11A104A25A11A103A59A65A65A111A11A103A59A80A104A65A84A11A103A59A80A104A11A104A119A11A103A59A82A111A65A65A33A11A103A80A65A65G990G17860比例G3800方，用直G5464为3G174MM的滴G3848G17839G15904滴制，G1209滴丸圆整度、黏结情况、G11840度、溶散G7114G19492为考察G6363标，试验结G7536见表5。A37A111A38A0A3A4A1A2A93A94A72A73A12A13A37A93A94A134A78A12A47A14A100A76A16A55A16A142A105A106A107A18A69A109A24A11A32A48A78A12A65A65A65A59A110A16A78A12A11A82A11A11A146A70A84A19A147A112A113A55A150A11A19A19A80A110A114A78A12A11A82A59A33A146A70A80A19A147A112A113A55A25A45A25A78A12A53A101A58A17A11A82A111A84A146A25A19A111A74A78A12A11A82A19A111A146A70A11A19A147A112A113A55A150A11A19A19A84A74A78A12A11A82A11A59A51A55A16A80A111A119A78A12A70A152A116A69A117A11A82A19A45A51A55A16A80A19A33A110A114A78A12A11A82A19A59A51A55A16A59A33G21G177G3冷凝液G9213度的考察G3G3G3G3G4570药物与基质按一G4462G18209比，G13634于80C水浴中加热熔融，80C保G9213，滴入不同G9213度的冷凝液中，滴G7754G990部选择G21040C，滴G7754G991部冷凝液G9213度分G2047为0CG1209G991，G205C，G200CG1209G990，考察滴丸的黏结情况和圆整度，结G7536见表6。G3A37A84A38A0A121A83A68A71A16A8A72A73A12A13A121A83A68A71A16A78A12A47A14A100A76A16A10A48A9A118A122A108A59A19A157A158A19A157A158A159A125A74A78A12A160A31A57A18A11A82A111A19A24A25A111A34A35A11A65A111A157A158A74A78A12A75A31A57A18A11A82A80A111A24A25A84A34A35A11A19A157A158A159A122A78A12A75A31A57A18A11A82A84A11A24A25A25A34A35A9A118A122A108A25A19A157A158A19A157A158A159A125A74A78A12A161A123A57A18A11A82A19A33A24A25A33A34A35A11A65A111A157A158A74A78A12A161A123A57A18A11A82A11A11A24A25A119A34A35A11A19A157A158A159A122A78A12A75A31A57A18A11A82A80A80A24A25A33A34A35滴G7754G990部G9213度影响滴丸的成型，G5415液滴G17839入冷凝液G990部G7114，较G20652的G9213度G1427于滴丸G1817分收缩G727G13792G20600G9994的低G9213使滴丸G17817速冷却，会使G2030从滴G3848滴G991的不G16280G2029拖尾滴来不G2462收缩G13792成类圆球形或G6165球形G12447即凝固，使滴丸形状不G16280G2029，有G7114有G8680G8885存在。G3G3G3G3滴G7754G991部的冷凝液G9213度对滴丸形状和黏结G12255度G1075有影响，特G2047是在G200CG1209G990G7114，滴丸不G14033G4448G1852冷却，形状G2476G6165，同G7114不G7041的滴丸G3546G12227一G17227G2530会G17908成黏结，G3593G3634出料口，使G10995G1147G7092法G17839G15904。G3G5415滴G7754G991部的冷凝液G9213度在0CG1209G991G7114，滴丸G20600G9994冷却，表面G12907G12973，且G11840度差，用G6175G14033G17743易G11784G11874开。所G1209G4466G19481G10995G1147G7114G9213度G6523制在G205G3C为G3921。G3G21G178G3丸G18337的影响G3252G13044考察G3G3G3G3考察液滴G9213度、滴制距离（滴G3848与冷凝液面的距离）、基质G18209比、滴G3848大小对滴丸G18337量的影响，结G7536见表7。A37A119A10A48A124A126A128A129A131A132A37G3A124A126A128A129A10A48A7A133A68A9A71A16A119A111CA25A45A34A35A0A64A93A94A70A119A111A157A158A9A36A61A49A33A111CA25A84A34A35A9A6A135A136A11A19A137A34A25A111A34A35A0A64A93A94A173A11A19A137A34A9A6A135A111A137A34A25A33A34A35A136A171A138A46A139A141A143A10A3A4A95A1A62A178A144A145A148A148A148A149A151A153A154A155A148A148A148A148A155A156A155A162A162A163A144A155A164A165A162A166A163A144A167A168A169A170A165A172A174A162A165A163A144A162A172A148A167A168A167A175A176A177A179A180A181A167A182A162A172A148A174A155A163A1443G3G16764G16782（G20）滴丸的G18337量G16757G12651G1856式G726G10714G16782丸G18337G21G177G85G164,G1866中G85为滴出口的G2334G5464，G164为药液的表面张力。从G990G1856式可G5483出，影响滴丸G18337量的G3252G13044G1039G16213有G1120G1022G726滴G3848大小、药液表面张力。G13792表面张力与G9213度和药液黏度相G1863。G10714G16782G990G16774，滴G3848口G5464越大，丸G18337G1075G3698大G727但G19555G11540滴G3848口G5464G3698大，药液难G1209G3647G1817G9397管口，G17908成药液滴不出，或丸量差G5334过大。G5415料液的G9213度降低，药液的黏度G3698加，使表面张力G3698大，丸G18337G3698加，所G1209试验中料液G9213度在70CG7114的丸G18337大。料液的G9213度过低G7114，会G4560G14280药液在管口G3800凝固，或发G10995滴丸表面不G16280G2029等现G16949，所G1209料液G9213度不G14033过低。G3（G21）滴丸的G1881G13870力可G1209用G1209G991G1856式表G12046G726G58CG21G164A183G727滴丸与冷凝液G19400的黏G19480力G58A184G164A185G14G164A186G14G164A185A186（G164A185G726液滴张力，G164A186G726冷凝液张力G164A185A186G726界面张力）G727滴丸形成力为G726G58CG58A184G164A185G164A186G164A185A186。从G990式G1856式中可见，选用界面张力小的冷凝液G2045于滴丸成型，可显著G6925G2904滴丸的圆整度。液体G11719G15605的表面张力大于G11014基G11801G8845，加G1055G1866黏度小，成型不G3921。G3（3）药物与基质的比例不同，成型和黏结情况G1075不同，G19555G11540基质的比例G3698大，G7368G3822的药物分G4388G17839入载体的G2379G7366G19154中形成分G4388分散体，降低药物G7424G17535的黏度，滴丸黏结G12255度G1955小，G7368易G20046G2045G10995G1147G727但基质比例G3698G3822G2530，药物G2559量降低，G19668G16213G3698大滴G3848来G3698G18337滴丸，可G14033G5114来G7044的G19394G20076，例如G7092法滴制、丸G18337差G5334过大等。G3（4）G11840G14038G18252的加入，降低G1114料液的黏度，使滴制G7368易G17839G15904，但G11107水性的G7460料对滴丸的溶散G7114G19492影响G19762G5132显著，G5062G17241过氯霉G13044滴丸G2000MIN的G6523制标准。G3（5）表面G8975性剂G55G90G72G72N80的加入，G14033G3827G6925G2904药物的溶G16311性，特G2047对G11840G14038G18252G5353G17227的G4861G16311G5322G17843有显著G6925G2904效G7536，滴丸G14033G3827在4050分G19059G1881溶散。但G2532G9213的加入，影响滴丸的圆整度，可G14033是G3252为降低G1114液滴的表面张力G2462G1881