离心造粒制备工艺

53Vol.5No.320075ChineseJournalofPharmaceuticsMay2007p.9420061106(1975),(),,;(1963),(),,,,,,Tel[phone],[e-mail](2007)03009408110016R964A0.5~2.5mm0.5~1.5mm-[1][2](CBZ)[3](L-HPC)1JBZ300()DGNA()()UV9100()SUNG150()(20060708)(HPMC5mP·22.195[4]0.3Nm3·h-112.5L·min-1560r·min-1(MCC)150g4min12mL·min-16mL·min-14min1g·min-10.3mL·min-15min250~425µm2.22.2.1(2005C)900mL(24mL1000mL)100r·min-160min5mL0.8µm2mL10mL2005(A)285nm1mg·mL-12mL50mL5mL25mL8µg·L-160min2.2.22.2.12mL50mL40µg·mL-11.63.24.88.011.212.8µg·mL-1-(2005A)285nm(A)(C)A=0.055C+0.006(R=0.9999)2.2.340.050.060.0mg6.48.09.6µg·mL-1285nmA3100.3%99.8%100.1%100.1%RSD0.3%2.2.48µg·mL-16RSD0.5%2.2.58µg·mL-102681224hRSD0.2%9652.324~302.3.1[1](1g)85%(Φ)Φ1.25cm(H)(r)tanθ=H/rθ()2.3.210mL()(=/)2.3.3m1(10g)25r·min-14min180µmm2Fr(%)=(m1m2)/m1×100%2.3.4()(24~30)2.42.4.1(250~425µm)50g3%(w/v)(HPMC)300r·min-13.5mL·min-11.0g·min-10.3Nm3·h-10.3Mpa10~20L·min-15min4012h24~3080%2.4.20.1mol·L-197pH=6.8200~300µg·mL-145minL-HPC[5]KLEINEBUDDKP[6]MCCL-HPCL-HPC()30%MCCL-HPCMCCL-HPC(15:85)311MCCL-HPC020406080100020406080t/minRelease/%CBZ-MCC3:7CBZ-LHPC-MCC3:6:1CBZ-LHPC(3:7)Fig.1TheeffectofdifferentdiluentsondissolutionprofilesofCBZpellets2.4.3L-HPC20%30%40%2L-HPC30%Fig.2Thesizedistributionofpelletsfromdifferentloadeddrug9852.4.41%(w/v)HPMC3%(w/v)HPMC5%(w/v)HPMC250mL3Fig.3Thesizedistributionofpelletsfromdifferentamountofadhesivesolution3301%(w/v)HPMC305%(w/v)HPMC243%(w/v)HPMC80%3%(w/v)HPMC2.5(A)(B)(C)(D)L9(34)1Table1FactorsandlevelsfororthogonaltestLevelsFactors123Rotorspeed(A)/(r·min-1)300350400Sprayspeed(B)/(mL·min-1)2.53.03.5Feedpowerspeed(C)/(g·min-1)0.51.01.5Ballingtime(D)/min357L9(34)[7](Φ)24~30YY2Φ299Table2TheorthogonaldesignandexperimentresultsTestNo.ABCDYΦYΦ1111165.218.228.82122279.517.245.13133369.213.542.24212365.215.434.45223176.217.541.26231257.620.3177313260.117.525.18321364.916.232.59332165.117.530.1j116.188.378.3100.1j92.6118.8109.687.2j87.789.3108.5109.1K138.729.426.133.4K230.939.636.529.1K329.229.836.236.4Rj9.510.210.17.32BCAD3%(w/v)HPMCA1B2C2D3300r·min-13.0mL·min-11.0g·min-17min333pHTable3Thepropertiesofthreebatchesofcarbamazepinepellets3BatchParameter123Φ()12.112.612.8θ()24.624.225.1Bulkdensity/g·mL-10.820.840.83Friability/%0.050.070.04Yield/%79.880.280.61005020406080100020406080t/minRelease/%water0.1mol/LHClpH6.8PBSFig.4ThedissolutionprofilesofCBZpelletsindifferentpHdissolutionmediumpH3a.-L-HPC20%1h50%-0.1mol·L-1pH=6.81h20%0.1mol·L-1pH=6.8-b.4MCCL-HPCpHc.VEROMMENJ[2][1].[M]..:,2005:448.[2]VERTOMMENJ,ROMBAUTP,KINGETR.Internalandexternalstructureofpelletsmadeinarotaryprocessor[J].IntJ101Pharm,1998,161(3):225236.[3][J]2006,14(4):232235.[4].[J]2002,19(6)399402.[5].[M].:,2004:340341.[6]KLEINEBUDDKP.Shrinkingandswellingpropertiesofpelletscontainingmicrocrystallinecelluloseandlowsubstitutedhydroxypropylcellulose:II.Swellingproperties[J].IntJPharm,2002,252(6):185192.[7],,,.[J].,2002,37(10)753755.PreparationofcarbamazepinepelletsbycentrifugalgranulatorYUShu-xiang,ZOUMei-juan,DENGChun-xia,FENGJin-hua,CHANGCui-eCHENGGang(SchoolofPharmacy,ShenyangPharmaceuticalUniversity,Shenyang110016,China)Abstract:ObjectiveTopreparecarbamazepinepellets.MethodCarbamazepinepelletswerepreparedbycentrifugationgranulationtechnology.Theinfluenceofformulationandprocessingvariablesonthesizedistributionandsphericityofpelletswereinvestigated.ResultsThekindoftheadhesiveagents,rotorrotationspeed,sprayingspeed,feedingpowerspeedandballingtimewerefoundtohaveremarkableinfluenceonsizedistribution.Thegrowthofpelletsweresignificantlyaffectedbythesprayingrateofbindersolutionandfeedingrateofpower.ConclusionThecentrifugationgranulationtechnologycanbeusedtopreparecarbamazepinepellets.Keywords:pharmaceuticscentrifugationgranulationtechnology;carbamazepinepellets;preparation;orthogonaldesign