[生物医药论文精品]玻璃化转变对中药喷雾干燥过程和产品质量的影响

玻璃化转变对中药喷雾干燥过程和产品质量的影响A1A0A3A4A2A4A2A3A3A5A6A7A8A9A10A11A12A13A14A15A16A17A18A19A20A21A22A23A24A25A26A27A28A29A30A31A3A3A32A7A8A9A10A11A33A34A35A36A37A38A39A40A41A42A43A44A45A15A16A17A18A46A47A48A49A12A22A23A24A25A26A27A28A40A50A51A52A53A54A55A56A57A58A59A60A21A22A23A24A25A26A34A61A29A62A63A3A15A16A17A18A46A47A48A49A56A54A55A21A57A58A59A60A64A12A22A23A26A7A8A9A10A11A65A66A67A27A28A29A62A68A62A68A3A3A69A70A7A8A9A10A11A71A32A72A73A13A14A15A16A17A18A46A47A40A72A74A57A75A76A77A40A78A79A22A23A24A25A29A80A81A82A81A82A81A82A3A3A7A8A9A10A11A83A13A14A15A16A17A18A83A46A47A48A49A83A22A23A24A25EFFECTSOFGLASSTRANSITIONONTHEPROCESSINGANDQUALITYOFTRADITIONALCHINESEMEDICINESPRAYDRYINGPRODUCTABSTRACTOBJECTIVETORESEARCHTHEEFFECTSOFGLASSTRANSITIONONTHEPROCESSINGANDQUALITYOFTRADITIONALCHINESEMEDICINESPRAYDRYINGMETHODSTOBASEONTHEGLASSTRANSITION,SINGLEFACTORINSPECTEDTHEEFFECTSOFSPRAYDRYINGPARAMETERSONTHEQUALITYOFPRODUCTS,ANDANALYZEDTHERELATIONOFEXCIPIENTA84STORAGECONDITIONANDPRODUCTQUALITYRESULTSTHESPRAYDRYINGTECHNOLOGICALPARAMETER,EXCIPIENTANDSTORAGECONDITIONHAVEANIMPORTANTINFLUENCEONGLASSTRANSITIONCONCLUSIONGLASSTRANSITIONCANBEUSEDTOPROMOTETHETECHNIQUEOFTRADITIONALCHINESEMEDICINESPRAYDRYINGA84IMPROVESTORAGEPERFORMANCEA84ANDENHANCEPRODUCTQUALITYKEYWORDSGLASSTRANSITIONA85TRADITIONALCHINESEMEDICINESPRAYDRYINGA85TECHNOLOGICALPARAMETERA85PRODUCTQUALITY无定形聚合物随着温度的升高可依次体现玻璃态（GLASSSTATE，又称无定形态、非晶态）、高弹态、粘流态三种力学状态，玻璃态和高弹态间的转变称为玻璃化转变（GLASSTRASITION），对应的转变温度为玻璃化温度TG。玻璃化转变并非高聚物特有的，比如食品中的糖类、脂类、蛋白质等就是常见的无定形基质1。中药浸膏普遍含有高比例的单糖、低聚糖及部分多糖，这些成分在生产和储存中会发生玻璃化转变，引起物料力学状态改变，进而能影响药物的物理、化学变化，对药品稳定性产生影响。比如喷雾干燥过程中黏壁、粘连，制剂过程中流动性差、粘冲，储存过程中结块、塌陷、结晶等等，这些问题实质上都是药品中无定形基质的玻璃化转变引起的。制何首乌G18267G6564物G993G7143干燥，G2572G9299性G5390，结块对温度G6947G5875，G1867有G980定的G1207G15932性，G6937G6117G1216G17885G6333制何首乌为G8181G3423G11752G12362玻璃化转变的影响。1药物与仪器制何首乌（G8839G2283G11477G5259G8978中药G7460有G19492G1856G2508）G727G10627G12958G12946（G19283G8813G5078G2338G5259G9108G12893G2390）G727LPGG12175G5527G5347喷雾干燥G7438（G8506进G5078G4403G8839制药G7438G7812G2390），G61G46G16G27G21G37G3423G11507G12366干燥G12677（上G9035G5078实G20576G1214G3132G5647G2390）。2方法和结果21方法G4570制何首乌G1100475G1069G18267G3250流G6564G24746H，G6922G19610G6564G2474G9094并G8999G13565G14279G4506度115G/ML，G9994G2530G6365G159321的G8503常G5049G14414G2454G6980喷雾干燥。G5465喷雾干燥稳定G2530，G1457G6357G1866G1194G5049G14414G7477G1226G993变，G6365G159321G3252G13044G16855G14422G14551G3272G8611次G16855G14422G1866中G980G20045G3252G13044进G15904G16809G20576。G16809G20576中浸膏G11004G18339G1209G4506度115G/MLG16757为G8611次30L，G10627G12958G12946G11004G18339为浸膏G3278含G18339的G11346分比，G6922G19610浸膏G12893并G13783G4531G1209G991G6363G7643G726粘连G11346分比G726喷雾干燥G7438的干燥G3624G1998G2487为粘连G20075G12902G1998G2487，G7071G20130分G12175G3132G1998G2487（G2375G19610G12893G3132）为G8503常浸膏G12893G1998G2487，G20075G12902G1998G2487物料G2356G5647G6922G19610浸膏G12893的G11346分比G2375为粘连G11346分比。G16825G6363G7643G2465G7156G1114干燥过程中G20075G12902间的粘连G5785G1929。G6922G10587G726G5647G6922G19610物料G235630L浸膏G3278含G18339的G11346分比。G16825G6363G7643主要G2465G7156G1114产品黏壁G5785G1929。水分G726G19610G12893G3132物料的水分，G6365药典水分测定法第G980法（烘干法）2检测。由于水分严重影响产品TG，G16825G6363G7643能G2465G7156产品玻璃化的质G18339。G2572G9299速度3G726G4570添加G10627G12958G12946的浸膏G12893置25，75RHG10627境G991，G8611隔G980段时间，称G18339并G16757算G2572G9299G11346分G10587，G1209时间和G2572G9299G11346分G10587作图，比较G1866G2572G9299速度。G16825G6363G7643主要G2465G7156G1114辅料对产品防潮效果的影响。A861A87A88A89A90A91A92A93A94A95A96A97A98A99A100A96A97A101A99A100A102A103A104A99A100A102A105A101A99A100A106A103A107A108A109TABLE1SPRAYDRYINGCONDITIONSEXTRACTUMDENSITY/GML1EXTRACTUMTEMPERATURE/A110FLOWRATEOFFEED/LMIN1INLETTEMPERATURE/A110EXCIPIENTCDCONTENT/NORMALPARAMETER11595071700REGULATIONOFTHEFACTORS105A111110A111115A111120A11112580A11185A11190A1119506A11107A11108A11109A11110140A111155A111170A111185A1112000A1115A11110A1111522结果A1121A113A114A115A116A117A118A119A120A121A122A123A124AA125A126A127A128A129A124BA125A126A127A130A129A124CA125A131A132A133A129A124DA125A131A134A130A129FIG1EFFECTSOFSPRAYDRYINGTECHNOLOGICALPARAMETERSA1122A135A132A121A122A123A124AA125A113A114A115A116A136A137A124BA125A126A127A138A139A140A133A129FIG2EFFECTSOFEXCIPIENTA124AA125ONDRYINGPROCESSINGA124BA125ONHYGROSCOPICITY3讨论31喷雾干燥G5049G14414G2454G6980的影响从图1可知，喷雾干燥各G5049G14414G2454G6980对干燥过程和产品质G18339都有影响，这种影响是通过浸膏中无定形基质的玻璃化转变实现的。图3描述G1114干燥过程产品水分和TG的关系4，整个过程中水分逐渐降低，TGG993断升高，最终形成玻璃体产品。图3G4570干燥过程分为四个阶段G726A雾化阶段，物料通过喷头雾化。B预热阶段，雾滴温度迅速升高G14279沸腾温度。C恒速干燥阶段，水分迅速蒸发，雾滴温度G1457G6357稳定，TG升高。D降速干燥阶段，水分G6357续降低使G20075G12902G15932面TG高于物料温度而形成玻璃体，G20075G12902内部剩余水分在高温G991逐步往外迁移。综合图1和图3进G980步分析G5049G14414G2454G6980如何通过玻璃化转变影响干燥过程和产品质G18339。浸膏G4506度G726体现G1114浸膏初始G3278含G18339。降速干燥阶段如果G20075G12902水分过高，往外迁移的水分会使G20075G12902G15932面G1457G6357粘弹态而发生粘连，而且大G18339的水分迁移会破坏G20075G12902G15932面的圆整度。G6564高浸膏G4506度降低G1114水分，可快速形成玻璃体而降低此阶段G20075G12902粘连，同时可减少水分蒸发对G20075G12902G15932面的破坏，对G6564高产品流动性有G980定意义。G6564高浸膏G4506度还可G6564高干燥效G10587，降低产品水分，使产品质G18339有所G6564高。但G4506度过高容G7143使喷头堵塞，降低产品G6922G10587。G1457温温度G726对G6922G10587和G8503常浸膏G12893的水分影响G993大，G1866影响主要在于降低料G9094的粘度，G6564高雾化效果。G1457温温度过低会使G20075G12902G3252雾化效果减弱而增大，在降速干燥阶段G1457留较高水分，增加粘连G11346分比，粘连G20075G12902往往含有较高水份，流动性较差，在储存中G7143软化粘连，G3252此应G6564高G1457温温度。4321TTTMOISTURECONTENT/DRYTIME/S1A141A142A143A144A145HOTAIRTEMPERATURE2A141A146A147A148A149MOISTURECONTENT3A141A146A147A144A145PRODUCTTEMPERATURE4A141A146A147TGPRODUCTTGA1503A151A152A153A154A155A156A157A158A159A160TGA161A162A163FIG3RELATIONSOFMOISTURECONTENTANDDRYINGTOTGTTEMPERATURE/A164ABCD进料速度G726进料速度增加使雾化效果降低，容G7143堵塞喷头，同时雾滴过重会造成甩壁，严重降低产品G6922G10587，G16855G14422喷头转速和喷头角度可G1209改善这些问题。但进料速度过高会大大减少蒸发面积，延G19283恒速干燥时间，并降低降速干燥效果，既增加G1114G20075G12902粘连，还使G8503常产品水分增高。G3252此生产中应当控制进料速度。进G20130温度G726升高进G20130温度可使产品水分进G980步降低，形成质G18339较高的玻璃体。但由于同时升高G1114G1998G20130温度，容G7143使降速干燥阶段的G20075G12902G15932面温度升高，尤G1866是低TG产品会再次进入粘弹态，造成严重的G20075G12902粘连和黏壁。但进G20130温度过低引起的问题更加严重，低温G991干燥效果差，产品水分过高，同样造成严重的黏壁和G20075G12902粘连G727G2375使未黏壁的产品，在储存中也会迅速结块无法使G11004。G3252此，对于低TG产品也应当G6564倡使G11004较高的进G20130温度，同时在干燥G3624G991部、分G12175G3132和G19610G12893G3132采G11004降温措施来解决问题。3G21辅料的影响由图G21可知添加G16G10627G12958G12946对产品质G18339和干燥过程有较大影响，这也是通过浸膏中糖类玻璃化转变实现的。糖类的TG主要受G1209G991G3252G13044影响G726（A）增塑剂G726糖类的增塑剂主要是水，水的TG为135，如图4所示，水分会大大降低糖类TG，通常水分G8611升高1体系TG会降低5104,5。但玻璃化药品的稳定性G993G1177G994水分含G18339有关，还G994水G8975度（AW）有关。YRJORG11752G12362G1931G1935干燥G14621G14695时发现多G6980样品的TGG994AW（25）的关系G13459性G14403G3921，如图5所示，G1866G1856G5347为6G726TG（92TGI）AWTGIG5347中AW为样品水G8975度，TGI为无水样品的TG。A1654A166A167A168TGA169A170A171A1655A166A167A172A173A168TGA169A170A171FIG4EFFECTOFMOISTURECONTENTONTGFIG5EFFECTOFWATERACTIVITYONTG（B）分G4388G18339G726分G4388G18339G17246大TGG17246高。由图4可知，糖类的TG随分G4388G18339增大而升高。G18267G6564和水G6564G18267G8797会G19512G2447浸膏中的多糖和低聚糖，使单糖比例升高，所G1209这类G6564G2474物TGG5468低。添加辅料可G1209通过G1209G991三个G7053面影响药品TGG726G980、防潮作G11004G726图2B中，添加G16G10627G12958G12946G7186G14891降低G1114药品G2572G9299速度，能G3827降低水分的影响。G1120、G6564高TGG726G9163合物的TG有如G991G1856G53477G726TGG155XITGIG5347中TGI为G13464分I的无水TG，XI为G13464分I的物质的G18339分G6980。G16G10627G12958G12946为G14901G14808糖的G983聚体，TG高于常见的单糖和G2464糖，能G3827G6564高浸膏G12893的TG。如图2A中较高G11004G18339的G16G10627G12958G12946G15441G9994增高G1114产品水分，但G20075G12902粘连和黏壁G2376变化G993大，G16840G7138添加辅料能G6564高浸膏G12893的玻璃化效果。三、改善水分分G5079G726糖类成分在降低AW的同时会增加药品的G2572G9299性，但G7588些糖类能G3827改善药品G5506G10627境中水分的分G5079。如G1095糖TG为101，在较高温度G991也能G1457G6357玻璃态，而G10988G19718G18267TG为10，G7143结晶而使水分转移G2533药物，G6937G2081G13785能G6564高药物热稳定性8。G9035G15311糖（TREHALOSE）是G14901G14808糖的G980种非还G2419G2464糖，TGG1781077，同时G1866结G7512可G1209G4565存药品中的水，在较高水分G991G1185能G1457G6357玻璃态，对G3809G7446生物大分G4388的G8975性也有G5468G3921的G1457G6264作G110045,9，是G980种G5468有G2081G7235的辅料。33储存G7477G1226的影响玻璃态的药物对水分G6947G5875性增加，更容G7143G2572G6922G10627境水分，随水分的升高TG迅速降低，TGG6521G17829G10627境温度G2375可引起物料发粘，G13485G14026G3230G9760G16025G6122G2399G10267G5114来G993G1427。TG进G980步降低还可引起物料变G14406、结块、塌G13565、结晶。G3252此G5529G20047严G7696控制玻璃态药品的水分，G993G1177要降低药品水分，还G19668控制储存G10627境G9299度，并采G11004防潮G2265G7460来减少水分的增G19283。温度是容G7143G15999G5585G11065的G3252G13044。喷雾干燥G2530G7411产品进入G19610G12893G3132中，积G6886G980定G6980G18339G2530分G16025G2265G16025。G19610G12893G3132温度会由于G16786G3803G1268热而升高，引起产品黏壁和结块G727产品G2265G16025时温度较高也会使G20075G12902内部水分迁移G2052G15932面，使产品在储存过程中粘连。G3252此，产品G2265G16025G2081G5529G20047G13475过降温G3800理，可通过G19610G12893G3132降温来实现这G980要G8726。G2375使采G2474G1209上措施，G980些浸膏G12893在低水分G991G1185发生结块，这是由于这些药品G7424G17535TG较低造成的，这类药品G5529G20047在G16280定的温度G991储存。G1119实上为G1114稳定产品质G18339，所有玻璃态药品都应G7138G11842G16280定储存温度。4结论与展望喷雾干燥G5049G14414G2454G6980、辅料和储G15267G7477G1226都对中药的玻璃化转变产生重要影响，通过G16855G14422G5049G14414G2454G6980和添加辅料可G1209G16855G14422TG，实现产品玻璃化，G6564高药品质G18339G727通过控制储G7477G1226，可G1209稳定玻璃化药品的质G18339。玻璃化转变理G16782G993G1177可G1209G6363G4560中药的喷雾干燥，改善药品质G18339和储存效果G727而且玻璃态药品还G1867有G5468多G10432特性质G726玻璃态物质体系粘度G178101012PAG103S1014PAG103S，体系的G14270由体积G4579，G17828动G19471力大，分G4388G3800于G15999G1935结状态，G7506G5359时间G1972G1058为无G12363大，使玻璃态药物分G4388G6205G6967速G10587和化学G2465应速G10587G7509低，G1867有G7509高的物理和化学稳定性，G3252此可G1209G7509大G3332G6564高药品稳定性。无定形态物质比结晶态有更高的G9354G1998速G10587，可G1209G6564高G19602G9354药物的药效。由于这些特G9869，使玻璃化理G16782在在更G5203G8879的制剂生产中也有G5468G3921的应G11004G2081G7235。A174A175A176A177A178A179A180A181A182A183A184A185A186A187A188A189A183A190A185A186A183A188A191A192A193A183A194A188A195A196A197A198A199A190A200A200A195A201A196A202A200A203A198A197A204A204A205A206A197A207A204A208A196A208A202A207A202A207A196A209A195A187A206A202A201A195A204A204A208A207A210A211A186A196A202A206A197A210A195A197A207A212A213A214A197A198A208A196A215A202A200A216A202A202A212A187A206A202A212A214A201A196A204A179A217A181A199A218A219A219A220A221A222A220A223A224A225A226A227A228A229A230A231A232A233A211A234A235A235A236A211A234A178A237A180A238A237A234A199A179A234A181A189A209A199A187A228A234A235A235A237A233A239A202A198A240A228A241A242A243A244A234A235A235A237A245A246A188A247A248A233A179A186A181A199A234A235A235A237A249A250A251A252A253A199A179A254A181A183A190A213A188A191A192A194A182A188A194A184A185A203A217A217A188A195A196A197A198A199A192A207A200A198A214A195A207A201A195A202A200A255A208A200A200A195A206A195A207A196A190A18A201A208A0A208A195A207A196A204A202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