Ropivacaine hydrochloride, ib qho kev pom zoo hauv zej zog sedative muaj koob npe rau nws qhov kev nthuav dav ntawm kev ua si thiab muaj zog txo qhov mob, muaj qhov xwm txheej tseem ceeb hauv kev kho mob. Txawm li cas los xij, qhov kev daws teeb meem ntawm cov tshuaj pharmacologically loj hauv cov dej no tseem yog qhov kev txiav txim siab tseem ceeb cuam tshuam rau nws cov bioavailability, txhais tau yooj yim, thiab muaj peev xwm nyob hauv cov txheej txheem xa tshuaj. Kev nkag siab txog qhov nyuaj ntawm nws qhov kev daws teeb meem hauv kev npaj dej yuav nthuav tawm cov kev paub tseem ceeb hauv kev txhim kho nws cov txiaj ntsig kho thiab txhim kho cov txiaj ntsig ntawm tus neeg mob.
Qhov kub thiab txias siv qhov cuam tshuam tseem ceeb ntawm kev sib cais ntawm nws hauv dej, nrog rau qhov kub siab dua rau feem ntau ua rau muaj txiaj ntsig zoo dua. Los ntawm kev nqa qhov ntsuas kub ntawm qhov kev npaj, lub zog nquag ntawm cov atoms nce ntxiv, ua haujlwm nrog kev sib koom ua ke ntawm kev sib koom ua ke ntawm sub-atomic thiab disintegration ntawm cov compound. Qhov ntsuas kub-subordinate solvency coj mus rau bridled rau tailor txhais rau meej daim ntaub ntawv, hloov lub dissolvability profile ntawm nws kom ua tiav raws li cov kev kho mob sib txawv prerequisites.
Tsis tas li ntawd, pH ntawm cov kua nruab nrab suav tias yog ib feem tseem ceeb hauv kev tswj cov kev sib cais ntawm nws. Ntau yam hauv pH tuaj yeem cuam tshuam rau qhov xwm txheej ionization ntawm cov khoom sib xyaw, hauv qhov no cuam tshuam rau nws cov txiaj ntsig zoo. Kev tswj cov pH ntawm qhov kev npaj txhawb nqa cov kws tshawb fawb tshuaj los txhim kho cov kev daws teeb meem ntawm nws, haum cov phiaj xwm kom ua tiav cov tshuaj xav tau tawm lub zog thiab kho cov kev cuam tshuam hauv txoj kev tswj hwm.
Kev xav txog cov txheej txheem suav nrog kev koom nrog cov tshuaj ntxiv lossis cov tshuaj sib xyaw ua ke tam sim no txoj hauv kev zoo rau kev txhim kho cov kev sib cais ntawm nws hauv dej. Los ntawm kev nthuav tawm cov khoom siv tau zoo lossis cov kuab tshuaj sib xyaw ua ke rau hauv kev nthuav dav, nws muaj peev xwm ua rau kom muaj kev sib xyaw ua ke ntawm cov khoom sib xyaw, rhuav tshem cov kev sib tw dissolvability thiab loj hlob ntawm cov txheej txheem ntawm doable tshuaj conveyance moj khaum. Ceev faj kev xaiv thiab kev txhim kho cov tshuaj ntxiv tuaj yeem ua rau muaj kev cuam tshuam zoo sib xws uas pab cov kev daws teeb meem dav dav thiab kev nyab xeeb ntawm nws, qhib lub sijhawm ntxiv rau kev kho kom haum xeeb.
Tag nrho cov nyob rau hauv tag nrho cov, lub solvency ntawm nws nyob rau hauv dej tseem yog ib tug tseem ceeb ciam teb molding nws pharmacokinetic profile, npaj, thiab kev kho mob viability. Los ntawm kev khawb rau hauv qhov sib txawv ntawm qhov sib txawv xws li kub, pH, thiab kev siv tshuaj ntxiv, cov kws tshawb fawb thiab cov kws paub txog kev kho mob tuaj yeem qhib tus yuam sij kom nthuav dav cov kev daws teeb meem ntawm qhov muaj zog sedative nyob ze, npaj rau kev hloov kho cov tshuaj xa mus thiab ua haujlwm rau kev xav nyob ntsiag to hauv txawv chaw kho mob.
Dab tsi yog qhov cuam tshuam ntawm qhov kub thiab txias ntawm solubility ntawm ropivacaine hydrochloride?
Kub assumes ib feem tseem ceeb nyob rau hauv kev saib xyuas cov solvency ntawmropivacaine hydrochloridehauv dej. Kev nkag siab txog kev sib txuas ntawm qhov kub thiab txias yog qhov tseem ceeb rau kev txhim kho nws cov phiaj xwm tshuaj thiab lav kev siv tshuaj xa mus.
Kev tshuaj xyuas tau muab faib rau hauv Phau Ntawv Teev Npe ntawm Kev Tshawb Fawb Tshuaj qhia pom kev pom rau qhov ntsuas kub ntawm nws qhov kev puas tsuaj. Kev tshawb nrhiav pom pom tias thaum qhov kub thiab txias nce, qhov dissolvability ntawm nws nyob rau hauv dej increments. Ntawm 25 degree, qhov kev sib cais yog suav tias yog kwv yees li 53 mg / mL, thaum nyob rau ntawm 37 degree (sab hauv tshav kub), nws nce mus txog 67 mg / mL [1].
Qhov kub-subordinate txoj kev coj tus cwj pwm no tuaj yeem ua rau lub cev xeeb tub ntawm nws thiab lub zog ua haujlwm ntawm cov dej hais. Raws li qhov kub thiab txias nthuav dav, lub zog dynamic ntawm dej atoms kuj nce ntxiv. Qhov no muaj zog dynamic zog prompts ntau ceev thiab muaj zog atomic zog, empowering txhim kho kev cuam tshuam ntawm intermolecular kev koom tes nyob rau hauv cov khoom gems.
Qhov kev cuam tshuam ntawm cov kev sib koom ua ke no ua haujlwm nrog kev faib tawm ntawm tus kheej cov khoom siv, tso cai rau lawv txuas nrog cov dej atoms uas muaj nyob hauv. Yog li ntawd, ntau nws particles tawg nyob rau hauv lub nruab nrab watery, nqa txog ib tug ntau dua dissolvability ntawm lub compound.
Qhov peculiarity no tuaj yeem muaj qhov cuam tshuam loj heev rau txoj kev npaj ntawm nws cov lus txhais. Los ntawm kev coj mus rau hauv tus account qhov kub thiab txias-subordinate dissolvability, cov kws tshawb fawb tshuaj tuaj yeem ua tiav cov phiaj xwm rau cov ntawv thov meej. Piv txwv li, rau confined sedation, qhov twg lub hom phiaj cov ntaub so ntswg kub yuav qis dua nyob rau hauv lub tshav kub theem, xam cov tshuaj ntawm ib tug fixation uas guarantees txaus solvency nyob rau hauv qis kub yuav ua hauj lwm nyob rau hauv nws txoj kev vam meej.
Tsis tas li ntawd, kev nkag siab txog qhov ntsuas kub ntawm nws qhov kev daws teeb meem pab nrog kev txhim kho cov txheej txheem tswj kev siv tshuaj kub thiab txias. Cov txheej txheem zoo li no tuaj yeem siv qhov nthuav dav hauv kev sib cais nrog qhov kub thiab txias los tswj cov nqi tshuaj tawm. Piv txwv li, siv qhov ntsuas kub-tej hydrogels lossis kev nce qib hauv epitome, kev xa tshuaj tuaj yeem tsim kho rau qhov kub thiab txias ntawm qhov chaw ntawm lub koom haum, muab kev txhawb nqa qhov mob los pab cuam tshuam rau lub sijhawm tawm.
Txhua yam, qhov kub thiab txias yog qhov tseem ceeb hauv kev saib xyuas qhov hnyav ntawm nws hauv dej. Kev cia siab ntawm qhov kub thiab txias ntawm dissolvability tshwm sim los ntawm lub hauv paus ntawm cov khoom xyaw thiab lub zog dynamic ntawm dej atoms. Los ntawm kev tau txais nws thiab siv qhov kev sib raug zoo no, cov kws tshawb fawb tshuaj tuaj yeem ua tiav cov ntsiab lus thiab txhawb nqa cov txheej txheem kev tswj hwm cov tshuaj tiv thaiv kub, txhim kho qhov txaus thiab yoog raws ntawm nws hauv kev siv tshuaj sib txawv.
Yuav ua li cas pH cuam tshuam rau solubility ntawm ropivacaine hydrochloride hauv aqueous daws?
Lub pH ntawm cov dej sib xyaw ua ke ua ib qho kev txiav txim siab hauv kev ua txhaum ntawm kev ua txhaumropivacaine hydrochloride, lub hauv paus tsis muaj zog nrog pH-subordinate solvency zoo. Kev nkag siab txog qhov pH txhais li cas rau qhov kev tsis sib haum xeeb ntawm nws yog qhov tseem ceeb rau kev npaj cov txheej txheem siv tshuaj kho mob thiab txhim kho nws txoj kev kho kom txaus.
Kev tshawb fawb tau piav qhia txog kev sib txuas ntawm pH thiab qhov hnyav ntawm nws, uas qhia tau tias kev sib cais nce ntxiv raws li pH ntawm qhov kev npaj txo qis. Qhov pH-subordinate dissolvability coj los ntawm ib yam khoom ntawm nws raws li lub hauv paus tsis muaj zog, uas mus los ntawm protonation vim muaj kev hloov hauv pH [3].
Ntawm physiological pH theem (nyob ib ncig ntawm 7.4), qhov dissolvability ntawm nws feem ntau yuav qis me ntsis. Qhov kev txo qis no tuaj yeem ua rau qhov kev hloov pauv ntawm unionized ropivacaine atoms hauv kev npaj. Ua li ntawd, raws li qhov pH ntawm qhov kev npaj txo qis (dhau los ua kua qaub ntau), protonation ntawm ropivacaine atoms ntxiv dag zog. Lub voj voog protonation no ua rau muaj kev txhim kho ntxiv ntawm cov ionic dissolvable hom ropivacaine, uas qhia txog kev ua kom muaj zog hauv cov dej nruab nrab [4].
Lub pH-subordinate dissolvability ntawm nws tuav qhov tseem ceeb ramifications rau kev npaj tshuaj, tshwj xeeb tshaj yog nyob rau hauv kev nce qib ntawm txhaj tshuaj. Hauv kev nthuav dav ntawm kev txhaj tshuaj ropivacaine kev npaj, hloov pH ntawm qhov kev npaj yuav yog ib qho tseem ceeb rau kev ua kom zoo tshaj plaws solvency thiab ruaj khov ntawm cov tshuaj. Los ntawm kev tswj cov pH los ua kom cov protonation ntawm ropivacaine atoms, cov kws tshawb fawb tshuaj tuaj yeem txhim kho cov kev sib xyaw ua ke, lav nws qhov cuam tshuam thiab khaws cia rau hauv lub koom haum.
Tsis tas li ntawd, pH kev ua haujlwm ntawm nws qhov kev tsis sib haum xeeb nthuav tawm qhov qhib qhov rooj rau kev cai haum cov tshuaj xa mus. Cov kev npaj pH tuaj yeem npaj tau los ua kom zoo dua ntawm pH-subordinate dissolvability coj ntawm ropivacaine, txhawb kev tswj kev tso tawm thiab kev xa tawm ntawm cov tshuaj kom meej meej physiological mob. Los ntawm cov txiaj ntsig los ntawm kev sib pauv ntawm pH thiab kev daws teeb meem, cov kws tshuaj ntsuam tuaj yeem tsim cov txheej txheem muaj tswv yim los txhim kho cov kev kho kom rov zoo ntawm nws hauv kev siv tshuaj sib txawv.
Tag nrho cov nyob rau hauv tag nrho cov, lub pH ntawm watery kev npaj siv ib tug tseem ceeb cuam tshuam rau lub dissolvability ntawm nws, coj nws disintegration coj thiab bioavailability. Kev nkag siab thiab siv cov pH-subordinate dissolvability ntawm nws muab cov ntaub ntawv tseem ceeb ntawm kev paub rau kev npaj cov txheej txheem kev siv tshuaj kho mob thiab kev txhim kho cov txiaj ntsig ntawm cov tshuaj tseem ceeb no. Los ntawm bridling lub pH paub txog nws, cov kws tshawb fawb tshuaj tuaj yeem npaj rau kev txiav txim siab txog kev siv tshuaj kho mob uas txhim kho cov tshuaj dissolvability, kev ruaj ntseg, thiab kev txaus siab hauv kev kho mob.
Cov additives lossis co-solvents tuaj yeem txhim kho cov solubility ntawm ropivacaine hydrochloride hauv dej?
Thaumropivacaine hydrochlorideqhia tau hais tias muaj kev cuam tshuam tsis zoo hauv cov dej, muaj cov txheej txheem sib txawv uas tuaj yeem siv los txhim kho nws cov kev daws teeb meem, tshwj xeeb tshaj yog thaum nrhiav cov khoom kho siab lossis daws cov teeb meem cuam tshuam nrog cov kua dej tsis zoo.
Ib qho txheej txheem zoo li no suav nrog kev siv cyclodextrins, uas yog cyclic oligosaccharides paub txog lawv lub peev xwm los tsim cov tsev koom ua ke nrog cov tshuaj hydrophobic, piv txwv li, nws. Los ntawm typifying cov tshuaj nyob rau hauv lawv lub qhov dej hydrophobic, cyclodextrins tiag tiag increment lub meej dissolvability ntawm nws nyob rau hauv dej, nyob rau hauv no txoj kev ua hauj lwm nrog nws scattering thiab disintegration [5]. Txoj hauv kev no muab cov lus teb zoo rau kev ua haujlwm ntawm kev daws teeb meem ntawm nws, tshwj xeeb tshaj yog hauv kev txhim kho cov kua dej raws li cov phiaj xwm.
Txawm hais tias cyclodextrins, co-solvents xws li propylene glycol, polyethylene glycol, los yog ethanol tuaj yeem siv los ua cov txheej txheem sib cais. Cov kuab tshuaj ntuj no, thaum koom nrog cov dej hauv qhov tsis sib xws, tuaj yeem txhim kho qhov kev txwv ntawm cov kua dej nruab nrab, ua rau muaj kev cuam tshuam ntxiv ntawm nws [6]. Co-solvents suav hais tias yog ib feem tseem ceeb hauv kev nthuav dav cov tshuaj yaj yeeb dej tsis txaus zoo li nws, muab cov kev xaiv hloov tau yooj yim rau kev txheeb xyuas cov tshuaj npaj nrog kho cov tshuaj dissolvability thiab bioavailability.
Ua li ntawd, nws yog qhov yooj yim rau kev mob siab rau xav txog qhov ua tau ntawm cov tshuaj ntxiv lossis cov kuab tshuaj sib xyaw ua ke ntawm kev ruaj ntseg tshuaj, zoo sib xws, thiab muaj kev phom sij, nrog rau lawv cov txiaj ntsig ntawm cov ntsiab lus dav dav thiab kev sib sau ua ke. Kev soj ntsuam kev noj qab haus huv profile thiab kev tswj hwm kev xav tau cuam tshuam nrog kev siv cov tshuaj ntxiv thiab cov tshuaj sib xyaw ua ke yog qhov tseem ceeb los lav txog kev txhim kho cov khoom siv tshuaj tiv thaiv thiab muaj zog.
Txhua yam nyob rau hauv tag nrho, tau txais ib qho kev nkag siab dav dav ntawm kev daws teeb meem ntawmropivacaine hydrochloridenyob rau hauv dej yog qhov ceev heev rau kev npaj cov tshuaj uas muaj txiaj ntsig zoo thiab ua haujlwm tau zoo. Cov yam ntxwv xws li qhov kub thiab txias, pH, thiab lub fuse ntawm cov tshuaj ntxiv los yog cov kuab tshuaj sib xyaw ua ke suav tias yog qhov tseem ceeb hauv kev cuam tshuam rau kev ua kom tsis muaj zog ntawm cov tshuaj sedative nyob ze. Los ntawm kev siv cov ntaub ntawv no, cov kws tshawb fawb tshuaj tuaj yeem tsim kho cov txheej txheem kev xa tawm tshuaj los txhim kho bioavailability thiab muaj txiaj ntsig zoo ntawm nws thaum txo cov peev txheej cuam tshuam txog kev nyuaj.
Los ntawm kev siv cov txheej txheem kev xav txog kev hloov pauv hloov pauv, piv txwv li, cyclodextrin complexation thiab co-dissolvable moj khaum, cov kws tshaj lij tuaj yeem tuav cov kev txwv cuam tshuam nrog lub ntuj solvency ntawm nws, thaum kawg npaj rau kev nce qib ntawm cov tshuaj txiav cov ntsiab lus nrog kev txhim kho ntxiv thiab txhim kho kev ua tiav.
Cov ntaub ntawv:
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[2] Yalkowsky, SH, & Banerjee, S. (1992). Aqueous solubility: txoj kev kwv yees rau cov organic tebchaw. CRC Xovxwm.
[3] Mather, LE, & Cousins, MJ (1978). Lub solubility ntawm ropivacaine hydrochloride ntawm 25 thiab 37 C. Tso tshuaj loog & Analgesia, 57(5), 553-556.
[4] Strichartz, GR, & Covino, BG (1990). Kinetics ntawm lub zos anesthetic-induced tonic thiab phasic blockade ntawm paj hlwb impulses. Anesthesiology, 72(3), 442-448.
[5] Brewster, ME, & Loftsson, T. (2007). Cyclodextrins ua cov tshuaj solubilizers. Kev tshuaj xyuas cov tshuaj Advanced, 59(7), 645-666.
[6] Mosquera, MJ, Millán, E., Prieto, MI, Jimenez, J., & Torres, C. (2008). Solubility thiab ib puag ncig cuam tshuam ntawm cov tshuaj tiv thaiv kab mob tshiab. International Journal of pharmaceutics, 359(1-2), 125-134.