SCformulations水懸浮劑SuspensionConcentrates海利爾農(nóng)藥論壇〔第十屆山東省農(nóng)藥信息交流會(huì)〕英國(guó)禾大公司SC水懸浮劑描述：固體顆粒懸浮于水中

Description:Solidparticlessuspendedinwater常見(jiàn)問(wèn)題Issues懸浮物質(zhì)與水之間存在密度差Densitydifferencebetweensuspendedmatterandwater如果原藥密度大于1克/毫升將形成沉淀

Willformsedimentifdensityis>1如果原藥密度大于1克/毫升將漂浮

Willfloatifdensityis<1根據(jù)斯托克斯定律：較小的粒徑是必須的Stokeslaw:smallparticlesarerequired怎樣獲得較小的粒徑Howtoobtainsmallparticles?怎樣保持粒子的懸浮穩(wěn)定性

Howtokeeptheparticlessuspended?結(jié)晶增長(zhǎng)CrystalgrowthFormulationbreakdownprocesses制劑被破壞的過(guò)程Reversible可逆的Irreversible不可逆的膏化沉淀絮凝相轉(zhuǎn)化聚結(jié)奧氏熟化Ca.i.small小粒徑Oswaldripening奧氏熟化A.I.haslimitedwatersolubility原藥在水中有一定的溶解度Solubilityofsmallparticleishigherthansolubilityoflargeparticle較小粒經(jīng)的溶解度大于較大粒經(jīng)的溶解度Ca.i.large大粒徑Ca.i.small小粒經(jīng)

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Ca.i.large大粒徑HowtopreventOswaldripening怎樣預(yù)防奧氏熟化的發(fā)生較窄的粒徑分布范圍

Narrowparticlesizedistribution還有其他的訣竅

Thereareothertricks:Verylimitedamountofdilutedoilinaqueousphase將一定量的油稀釋到水相中

TomakeanSC水懸浮劑制備Preparationofsmallparticles小粒子的制備PreventingflocculationPreventingsedimentationTomakeanSC水懸浮劑制備Preparationofsmallparticles

小粒子的制備Smallsuspendedparticlesarepreparedbymillingprocess通過(guò)砂磨設(shè)備獲得較小粒徑Processingconditionsareimportant生產(chǎn)工藝條件很重要TomakeanSC水懸浮劑制備Preparationofsmallparticles小粒子的制備Milling砂磨Wetting->Dispersion->stabilization

潤(rùn)濕—分散—穩(wěn)定性Issueduringmillingprocess

砂磨過(guò)程中出現(xiàn)的問(wèn)題Duringmillingprocessfreshsurfaceisgenerated>砂磨過(guò)程中新的粒子外表產(chǎn)生Freshsurfaceisgenerallyofnon-polarnatureenwillclustertogetherrapidly>新產(chǎn)生的非極性的外表通常是的自然對(duì)開(kāi)很容易迅速聚集Thiscouldleadtoincreasedviscosityandevenmillblockage>這可能導(dǎo)致粘度增加甚至阻礙砂磨進(jìn)程Toovercomemillblockageawettingagentisneeded>為了克服這一問(wèn)題所以潤(rùn)濕劑的參加是非常必要的TomakeanSC水懸浮劑制備PreparationofsmallparticlesPreventingflocculation絮凝的預(yù)防PreventingsedimentationHowtopreventflocculation?

怎樣預(yù)防絮凝的產(chǎn)生Useofdispersants分散劑的使用DispersantshouldbefirmlylockedonsubstrateAnchoring錨固作用Dispersanttypes:分散劑種類Anionic陰離子Electrostaticstabilisation靜電穩(wěn)定作用CaDDBS/NaDDBS〔十二烷基苯磺酸鈣/鈉〕Fosfateesters〔磷酸酯類〕Nonionic非離子Stericstabilisation空間位阻穩(wěn)定作用Alcoholetoxylates〔乙氧基醇醚類〕Polymericdispersants〔高分子外表活性劑〕MixofthetwoElectrostericstabilisation混合靜電/空間位阻Naphtalenecondensatesulfonates(萘磺酸鹽甲醛縮合物)Ligninsulfonates〔木質(zhì)素磺酸鹽類〕ElectrostaticStabilization

靜電排斥作用GhGmaxElectrostatic靜電學(xué)Electrosteric靜電空間GhGh

2dM

h

Ghd2dp

Monomer單體-Polymer高分子StericStabilization空間位阻作用空間位阻是由于非離子表里面活性劑和/或高分子外表活性劑提供的Stericbarriersareproducedbyadsorptionofnonionicsurfactantsand/orpolymericsurfactant由于鏈的不利交叉排斥和熵值作用對(duì)重大交疊的影響RepulsionisduetounfavourablemixingofthechainsandentropiceffectsonsignificantoverlapFunctionsofsurfactants

外表活性劑的功能Wet潤(rùn)濕Disperse分散Functionsofsurfactants

外表活性劑的功能Wet潤(rùn)濕作用Dynamicmoleculestowetsurfaceduringmillingstage在砂磨期間動(dòng)態(tài)分子潤(rùn)濕新鮮的外表Smallermolecules分子量較小Negativeregardingstability對(duì)穩(wěn)定性有負(fù)面影響Disperse分散作用Largermoleculestostabilisesuspendedparticles大分子對(duì)粒子提供穩(wěn)定的懸浮支撐作用Actslow作用進(jìn)程緩慢Sizedoesmatter

分子大小關(guān)系DispersedPhase

分散內(nèi)相CONVENTIONALDISPERSANT

常規(guī)分散劑POLYMERICDISPERSANT

高分子分散劑DispersedPhase

分散內(nèi)相2dM

h

Ghd2dp

Monomer單體-Polymer高分子StericStabilization空間位阻作用空間位阻是由于非離子表里面活性劑和/或高分子外表活性劑提供的Stericbarriersareproducedbyadsorptionofnonionicsurfactantsand/orpolymericsurfactant由于鏈的不利混合排斥和熵值作用對(duì)重大交疊的影響RepulsionisduetounfavourablemixingofthechainsandentropiceffectsonsignificantoverlapRheologyprofilewettingagentvs.polymericdispersant

潤(rùn)濕劑與高分子分散劑流變性特征比照Wettingagent

潤(rùn)濕劑

Polymericdispersant高分子分散劑

Nosheareffectpolymericdispersantflowcurve:suspensionisproperlystabilized高分子分散劑在剪切作用下的流變曲線無(wú)影響：懸浮液相對(duì)穩(wěn)定

Wettingagentflowcurveincreaseshugelyatlowshear:insufficientstabilisation潤(rùn)濕劑在低剪切作用下的流變曲線明顯增大：不夠穩(wěn)定

Ifwettingagentisrequired,useatlowpossibleconcentration!如果潤(rùn)濕劑是必須添加的，盡可能在最低添加量下使用TomakeanSC水懸浮劑制備PreparationofoildropletsinwaterPreventingcoalescencePreventingsedimentation沉淀的預(yù)防Stokeslaw斯托克斯定律

Vs=velocityofsettling/creaming粒子沉降速度，cm/s;η=viscosity

水懸浮劑粘度，Pa.S;g=gravity

重力加速度，cm/s;r=radiusofsphere

分散介質(zhì)粒子直徑，cm;Δδ=densitydifferencesphere&continuousphase

分散粒子的密度與水的密度差Vs=--------------------9η2gr2ΔδStokeslaw斯托克斯定律

Vs=--------------------9η2gr2ΔδNosedimentationifdensityofsuspendedmatterandwaterphaseareequal如果懸浮介質(zhì)和水相之間沒(méi)有密度差，沉淀問(wèn)題就不可能發(fā)生固相/液相密度差=0Stokeslaw斯托克斯定律

Vs=--------------------9η2gr2ΔδThesmallertheparticlesize,thelessersedimentation粒徑越小沉淀越慢Notethisasquarefunction值得注意的是稱將速度與粒徑的平方正相關(guān)10timestheparticlesizeis100timesfastersedimentation10倍的粒徑大小差異將導(dǎo)致100倍的沉降速度差異粒徑大小Stokeslaw斯托克斯定律

Vs=--------------------9η2gr2ΔδIncreasedviscositywillreducesedimentation提高粘度有利于減少沉降Howeverviscositycannotbeincreasedinfinitely然而粘度不可能被無(wú)限制的增加Needofshearthinningrheologymodifier需要使界面內(nèi)剪切力變小的流體改性物XanthanorKelzanGumprovidesthiseffect黃原膠可以提供這種作用體系粘度RheologyprofileKelzangum

黃原膠的流變學(xué)特征粘度轉(zhuǎn)速SC水懸浮劑Generalformula:一般配方組成

成份用量Suspendedphase 分散相

40%Dispersant分散劑

4%Wettingagent潤(rùn)濕劑

0.5%Glycerine

防凍劑

5.2%Antifoam消泡劑

0.1%Preservative防腐劑

0.1%Kelzangum增稠劑

0.1%Water水

50%Issue:longtermstabilityandemulsionstabilityupondilution問(wèn)題：經(jīng)時(shí)穩(wěn)定性和乳液的稀釋穩(wěn)定性CrodaSCrecommendation

英國(guó)禾大公司在水懸浮劑方面的核心產(chǎn)品Dispersants:分散劑

Atlox4913羧酸鹽枝接物 AtloxMetasperse100L羧酸鹽修飾物 AtloxMetasperse500L羧酸鹽修飾物Codispersant/wettingagent:助分散劑/潤(rùn)濕劑

AtlasG-5000高分子嵌段共聚物 AtlasG-5002L高分子前段共聚物 Atlox4894高分子前段共聚物

Traditionalwettingagent:傳統(tǒng)潤(rùn)濕劑

SynperonicA7聚氧乙烯醇醚

Furtherguidelines使用說(shuō)明Dispersantlevel10%ofdispersedphase

分散劑的用量通常是分散內(nèi)相的10%30%dispersedphase30%的分散內(nèi)向3%totalsurfactants需要3%的總的分散劑Ratiodispersant/co-dispersant:2:1分散劑和助分散劑的比例為2：12%Atlox4913分散劑1%Atlox4894助分散劑Withtraditionalwettingagent:配以傳統(tǒng)的潤(rùn)濕劑2%Atlox4913分散劑1%AtlasG-5002L助分散劑MinimumamountSynperonicA7最小量的潤(rùn)濕劑Withtraditionalwettingagent

傳統(tǒng)的潤(rùn)濕劑用量確實(shí)定Optimumapproach:最理想的途徑——三元復(fù)配組合12345678910111213

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