Munyori / 1,2 Hu Rong 1 Hol ngoma Drum Song Xuezhi before the 1 tour Jinsong 1 – The new 1, 2
【Abstract】 Borosilicate girazi chinhu chinoshandiswa zvakanyanya kurongedza zvinhu uye mhinduro muindasitiri yemishonga.Kunyange zvazvo iine maitiro ekupikisa kwepamusoro, zvakadai sekutsetseka, kusagadzikana kwemarara uye kusapfeka, maion simbi uye silanol mapoka ari mugirazi yeborosilicate anogona kuramba achipindirana nemishonga.Mukuongorora kwemishonga yemakemikari nepamusoro pekuita liquid chromatography (HPLC), iyo yakajairika jekiseni vial iborosilicate girazi.Nekuferefeta mashandiro eHPLC egirazi mabhodhoro emhando nhatu pakugadzikana kwesolifenacin succinate inova isina kusimba alkaline komboni, zvakaonekwa kuti adsorption kune alkaline mishonga yaivepo mumagirazi egirazi anogadzirwa nevagadziri vakasiyana.Iyo adsorption yainyanya kukonzerwa nekudyidzana kweprotonated amino uye dissociative silanol boka, uye kuvapo kwe succinate kwakasimudzira.Kuwedzerwa kwehydrochloric acid kunogona kusvibisa mushonga kana kuwedzera chikamu chakakodzera cheorganic solvents kunogona kudzivirira kushambadza.Chinangwa chebepa iri ndechekuyeuchidza mabhizinesi ekuyedza zvinodhaka kuti atarise kudyidzana pakati pemishonga yealkaline negirazi, uye kuderedza kutsauswa kwedata uye basa rekuferefeta rekutsauka kunokonzerwa nekushaikwa kweruzivo rweadsorption hunhu hwemabhodhoro egirazi mukati. nzira yekuongorora zvinodhaka.
Mazwi akakosha: Solifenacin succinate, amino boka, HPLC magirazi egirazi, adsorb
Girazi sechinhu chekuputira chine zvakanakira kutsvedzerera, kubviswa kuri nyore uye kuomarara kuramba.Corrosion, kupfeka kusagadzikana, kugadzikana kwevhoriyamu uye zvimwe zvakanakira, saka inoshandiswa zvakanyanya mukushandiswa kwemishonga.Girazi remushonga rakakamurwa kuita sodium karusiyamu girazi uye borosilicate girazi, zvichienderana neakasiyana zvikamu zvaari.Pakati pavo, soda lime girazi rine 71% ~ 75% SiO2, 12% ~ 15% Na2O, 10% ~ 15% CaO;borosilicate girazi rine 70% ~ 80% SiO2, 7% ~ 13% B2O3, 4% ~ 6% Na2O uye K2O uye 2% ~ 4% Al2O3.Borosilicate girazi ine yakanakisa makemikari kuramba nekuda kwekushandiswa kweB2O3 pachinzvimbo chezhinji cheNa2O neCaO.
Nekuda kwehunhu hwayo hwesainzi, yakasarudzwa semudziyo mukuru wemushonga wemvura.Nekudaro, boronSilicone girazi, kunyangwe nekupikiswa kwayo kwakanyanya, inogona kuramba ichipindirana nemishonga, Pane nzira ina dzinowanzoita senge dzinotevera [1]:
1)Ion kuchinjana: Na+, K+, Ba2+, Ca2+ mugirazi inochinjanisa ion neH3O+ mumhinduro, uye pane kuita pakati peiyoni yakatsinhaniswa nemushonga;
2)Glass dissolution: Phosphate, oxalate,Citrates uye tartrates zvinomhanyisa kuparara kwegirazi uye kukonzera silicides.uye Al3+ inoburitswa mumhinduro;
3) Corrosion: EDTA iripo mumhinduro yezvinodhaka (EDTA) inogona kuomarara neiyo divalent ion kana trivalent ions mugirazi.
4) Adsorption: Pane rakaputsika Si-O bond pamusoro girazi pamusoro, anogona adsorb H+
Kuumbwa kweOH- kunogona kuumba hydrogen zvisungo nemamwe mapoka mumushonga, zvichiita kuti mushonga uwedzere kune girazi pamusoro.
Mazhinji makemikari ane mashoma ekutanga amine mapoka, Kana uchiongorora makemikari emishonga ane yakakwira performance liquid chromatography (HPLC), iyo inowanzoshandiswa HPLC autosampler vial iyo inogadzirwa negirazi reborosilicate, uye kuvapo kweSiO- pagirazi pamusoro kuchabatana neprotonated amine boka. , kubvumira kuwanda kwezvinodhaka kuderera, mhedzisiro yekuongorora ichave isina kururama, uye laboratori OOS (Kunze kweKutsanangurwa).Mumushumo uyu, iyo isina kusimba yakakosha (pKa ndeye 8.88[2]) mushonga solifenacin succinate (yakarongeka formula inoratidzwa muMufananidzo 1) inoshandiswa sechinhu chekutsvagisa, uye pesvedzero yeamber borosilicate majekiseni egirazi mabhodhoro pamusika pakuongorora zvinodhaka. inoferefetwa., uye kubva pane imwe nzvimbo yekuongorora kutsvaga mhinduro kune adsorption yemishonga yakadaro pagirazi.
1.Test chikamu
1.1Zvishandiso uye zvishandiso zvekuedza
1.1.1 Equipment: Agilent Yakanyanya Kubudirira ine UV Detector
Liquid chromatography
1.1.2 Zvishandiso zvekuedza: Solifenacin succinate API yakagadzirwa neAlembic
Pharmaceuticals Ltd. (India).Solifenacin standard (99.9% kuchena) yakatengwa kubva kuUSP.ARgrade potassium dihydrogen phosphate, triethylamine, uye phosphoric acid zvakatengwa kubva kuChina Xilong Technology Co., Ltd. Methanol neacetonitrile (zvose HPLC giredhi) zvakatengwa kubva kuSibaiquan Chemical Co., Ltd. Polypropylene (PP) mabhodhoro akatengwa kubva kuThermoScientific (US) , uye 2ml amber HPLC mabhodhoro egirazi akatengwa kubva kuAgilent Technologies(China) Co., Ltd., Dongguan Pubiao Laboratory Equipment Technology Co., Ltd., uye Zhejiang Hamag Technology Co., Ltd. (A, B, C inoshandiswa pazasi kumiririra kwakasiyana mabviro egirazi mabhodhoro, zvichiteerana).
1.2HPLC yekuongorora nzira
1.2.1Solifenacin succinate and solifenacin free base: the chromatographic column isphenomenex luna®C18 (2), 4.6 mm × 100 mm, 3 µm.Ne phosphate buffer (inoyera 4.1 g yepotassium dihydrogen phosphate, inoyera 2 ml ye triethylamine, wedzera kune 1 L yemvura yakanyanyisa, kurudzira kunyunguduka, usephosphoric acid (pH yakagadziridzwa kusvika 2.5) -acetonitrile-methanol (40:30:30) sechikamu che mobile,
Mufananidzo 1 Structural formula ye solifenacin succinate
Mufananidzo 2 Kuenzaniswa kwenzvimbo dzepamusoro dzemhinduro imwechete ye solifenacin succinate muPP mabhodhoro uye magirazi egirazi kubva kune vatatu vanogadzira A, B, uye C.
kupisa kwembiru kwaive 30 ° C, kuyerera kwaive 1.0 mL / min, uye vhoriyamu yejekiseni yaive 50 mL, Iyo yekuona wavelength i220 nm.
1.2.2 Succinic acid sample: kushandisa YMC-PACK ODS-A 4.6 mm × 150 mm, 3 µm column, 0.03 mol/L phosphate buffer (yakagadziridzwa kuita pH 3.2 nephosphoric acid) -methanol (92:8) sechikamu chenhare, kuyerera chiyero 1.0 mL/min, kupisa kwembiru 55 °C, uye vhoriyamu yejekiseni yaive 90 mL.Chromatograms yakawanikwa pa204 nm.
1.3 ICP-MS yekuongorora nzira
Zvinhu zviri mumhinduro zvakaongororwa pachishandiswa Agilent 7800 ICP-MS system, iyo yekuongorora modhi yaive He mode (4.3mL/min), iyo RF simba yaive 1550W, iyo plasma gasflow rate yaive 15L/min, uye inotakura gasi yekuyerera. yaiva 1.07mL/min.Iyo tembiricha yemukamuri yemhute yaive 2 ° C, iyo peristaltic pombi yekusimudza / kudzikamisa kumhanya yaive 0.3 / 0.1 rps, sampuli yekudzikamisa yaive 35 s, sampuli yekusimudza nguva yaive 45 s, uye kuunganidzwa kwakadzika kwaive 8 mm.
Kugadzirira kwemuenzaniso
Solifenacin succinate solution: yakagadzirwa nemvura yakanyanyisa, iyo concentration ndeye 0.011 mg/mL.
1.4.2 Succinic acid solution: yakagadzirirwa nemvura ye-ultrapure, iyo inosungirirwa ndeye 1mg / mL.
1.4.3 Solifenacin solution: dissolve solifenacin succinate mumvura, sodium carbonate yakawedzerwa, uye mushure mokunge mhinduro yakashandurwa kubva kune isina ruvara tomilky white, ethyl acetate yakawedzerwa.Iyo ethyl acetate layer yakabva yapatsanurwa uye thesolvent yakaitwa evaporated kuti ipe solifenacin.Nyura huwandu hwakakodzera hwesolifenacin inethanol (ethanol inoita m 5% mumhinduro yekupedzisira), wozonyungudusa nemvura kugadzirira mhinduro ine 0.008 mg/mL solifenacin (ine solifenacin succinate solution iri mumushonga wakafanana nesolifenacin. concentration).
Migumisiro uye Hurukuro
· · · · · · ················································· ··
2.1 Adsorption kugona kweHPLC mabhodhoro emhando dzakasiyana
Bvisa iyo yakafanana aqueous solution ye solifenacin succinate muPP vials uye 3 mhando dzeautosampler vials dzakabaiwa panguva dzakasiyana munzvimbo imwechete, uye nzvimbo yepamusoro peak huru yakanyorwa.Kubva pane zvakabuda muMufananidzo 2, zvinogona kuonekwa kuti nzvimbo yepamusoro yePP vials yakagadzikana, uye hapana inenge isina kuchinja mushure me44 h. Nepo nzvimbo dzepamusoro dzemhando nhatu dzegirazi dzegirazi pa0 h dzaive duku kudarika PP bhodhoro. , uye nzvimbo yepamusoro inoramba ichiderera panguva yekuchengetedza.
Mufananidzo 3 Shanduko munzvimbo dzakakwirira dze solifenacin, succinic acid, uye solifenacin succinate aqueous solutions dzakachengetwa mubhodhoro regirazi uye PP vials.
Kuenderera mberi nekudzidza chiitiko ichi, solifenacin, succinate acid, Aqueous solutions of solifenacin acid uye succinate mubhodhoro regirazi remugadziri Band PP mabhodhoro kuti aongorore shanduko yenzvimbo yepamusoro nenguva, uye panguva imwe chete girazi.
Mhinduro nhatu mumabhodhoro dzakasanganiswa nekushandisa Agilent 7800 ICP-MSplasma mass spectrometer yekuongororwa kwekutanga.Iyo data iri mumufananidzo 3 inoratidza kuti muGlass mabhodhoro mune aqueous medium haina adsorb succinic acid, asi adsorbed solifenacinFree base uye solifenacin succinate.Magirazi egirazi adsorb succinate.Huyero hwelinacin hwakasimba kupfuura hwesolifenacin isina base, panguva yekutanga Solifenacin succinate uye solifenacin yemahara base mumidziyo yegirazi.Mareshiyo enzvimbo dzepamusoro-soro dzemhinduro dziri mumabhodhoro ePP dzaive 0.94 uye 0.98, zvichiteerana.
Zvinowanzotendwa kuti pamusoro pegirazi silicate inogona kutora imwe mvura, iyo imwe mvura inosanganiswa neSi4 + muchimiro cheOH mapoka kuti aite mapoka e silanol Mukugadzirwa kwegirazi reoxide, maion polyvalent haakwanisi kufamba, asi alkali simbi (yakadai se Na + ) uye alkaline pasi simbi ions (yakadai seCa2 +) inogona kufamba kana mamiriro ezvinhu achibvumira, kunyanya alkali simbi ions iri nyore kuyerera, inogona kuchinjana neH + adsorbed pamusoro pegirazi pamusoro uyeKuendesa kune girazi pamusoro kuumba silanol mapoka [3-4].Naizvozvo, iyo H + yekumisikidza yeKuwedzera inogona kusimudzira ion kuchinjanisa kuwedzera mapoka e silanol pane girazi pamusoro.netafura1 inoratidza kuti zviri muB, Na, uye Ca mumushonga zvinosiyana kubva kumusoro kusvika pasi.succinic acid, solifenacin succinate uye solifenacin.
muenzaniso B (μg/L) Na(μg/L) Ca(μg/L) Al(μg/L) Si(μg/L) Fe(μg/L)
mvura 2150 3260 20 Hapana Kuonekwa 1280 4520
Succinic acid solution 3380 5570 400 429 1450 139720
Solifenacin Succinate Solution 2656 5130 380 No Detection 2250 2010
solifenacin mhinduro 1834 2860 200 Hapana Kuonekwa 2460 Hapana Kuonekwa
Tafura 1 Elemental concentrations ye solifenacin succinate, solifenacin uye succinic acid aqueous solutions yakachengetwa mubhodhoro regirazi kwemazuva masere.
Mukuwedzera, inogona kuonekwa kubva kune data muTable 2 kuti mushure mekuchengetedza mumabhodhoro egirazi kwe24 h, iyo yakanyungudutswa Iyo pH yemvura yakasimuka.Ichi chiitiko chiri pedyo zvikuru nedzidziso iri pamusoro
Vial No. Recovery rate mushure mekuchengetedza mugirazi kwe71 h
(%) Recovery rate mushure mekunge PH yagadziriswa
Vial 1 97.07 100.35
Vial 2 98.03 100.87
Vial 3 87.98 101.12
Vial 4 96.96 100.82
Vial 5 98.86 100.57
Vial 6 92.52 100.88
Vial 7 96.97 100.76
Vial 8 98.22 101.37
Vial 9 97.78 101.31
Tafura 3 Desorption mamiriro e solifenacin succinate mushure mekuwedzera asidi
Sezvo Si-OH iri pamusoro pegirazi inogona kuparadzaniswa muSiO-[5] pakati pepH 2 ~ 12, nepo solifenacin inoitika N munzvimbo ine acidic Protonation (yakayerwa pH yeaqueous solution ye solifenacin succinate ndeye 5.34, pH kukosha kwe solifenacin mhinduro ndeye 5.80), uye musiyano pakati pekubatana kweHydrophilic kunotungamirira kune zvinodhaka adsorption pamusoro pegirazi repamusoro (Fig. 3), solifenacin yakashambadzirwa zvakanyanya nekufamba kwenguva.
Pamusoro pezvo, Bacon naRaggon [6] vakawanawo kuti mumhinduro isina kwayakarerekera, hydroxy acids ine hydroxyl boka iri pachinzvimbo chakaenzana neboka recarboxyl Mishonga yemunyu inogona kubvisa oxidized silicion.Muchimiro chemolecular ye solifenacin succinate, pane boka rehydroxyl rine hukama nenzvimbo yecarboxylate, inorwisa pagirazi, SiO2 inotorwa uye girazi rinonyungudika.Nokudaro, mushure mekugadzirwa kwemunyu ne succinic acid, kuiswa kwe solifenacin mumvura kunotonyanya kuoneka.
2.2 Nzira dzekudzivirira adsorption
Nguva yekuchengetedza pH
0h 5.50
24h 6.29
48h 6.24
Tafura 2 pH shanduko yeaqueous solutions ye solifenacin succinate mumabhodhoro egirazi
Kunyange zvazvo PP vials isingasviki solifenacin succinate, Asi panguva yekuchengetedza mhinduro muPP vial, mamwe mapeji ekusachena anogadzirwa uye Kuwedzera kwenguva yekuchengetedza zvishoma nezvishoma kunowedzera kusvibiswa kwepamusoro nzvimbo, iyo yakakonzera kukanganisa pakuonekwa kwepamusoro pepamusoro. .
Naizvozvo, zvinodikanwa kuongorora nzira inogona kudzivirira girazi adsorption.
Tora 1.5 mL ye solifenacin succinate aqueous solution mubhodhoro regirazi.Mushure mekuiswa mumhinduro ye71 h, mitengo yekudzoreredza yaive yakaderera.Wedzera 0.1M hydrochloric acid, gadzirisa pH kusvika inenge 2.3, kubva kune data iri muTebhu 3. Zvinogona kuonekwa kuti mazinga ekudzorera ose akadzokera kumazinga akaenzana, zvichiratidza kuti adsorption storagetime reaction inogona kudziviswa pa pH yakaderera.
Imwe nzira ndeyekudzikisa adsorption nekuwedzera organic solvents.Ita 10%, 20%, 30%, 50% methanol, ethanol, isopropanol, acetonitrile yakagadzirirwa pamusangano we 0.01 mg/mL muSolifenacin succinate liquid.Mhinduro dziri pamusoro dzakaiswa mumidziyo yegirazi uye PP mabhodhoro, zvichiteerana.Pakamuri tembiricha Kugadzikana kwayo kwakadzidzwa kunoratidza.Tsvagiridzo yakawana kuti yakawandisa organic solvent haigone kudzivirira adsorption, nepo organic solvent yakawandisa solvent inotungamira kune isina kujairika peak chimiro chepamusoro peak nekuda kwekunyungudika.Chete zvine mwero organic zvinonyungudutsa zvinogona kuwedzerwa kuti zvinobudirira kudzivirira succinic acid Solifenacin is adsorbed pagirazi, wedzera 50% methanol kana ethanol kana 30% ~ 50% acetonitrile inogona kukunda kusimba kwekudyidzana pakati pemushonga nepamusoro pebhodhoro.
PP Mabhodhoro eGlass Mabhodhoro Girazi Mabhodhoro Girazi Mabhodhoro
Nguva yekuchengeta 0h 0h 9.5h 17h 48h
30% acetonitrile 823.6 822.5 822 822.6 823.6
50% acetonitrile 822.1 826.6 828.9 830.9 838.5
30% isopropanol 829.2 823.1 821.2 820 806.9
50% ethanol 828.6 825.6 831.4 832.7 830.4
50% methanol 835.8 825 825.6 825.8 823.1
Tafura 4 Mhedzisiro yeakasiyana organic solvents pane adsorption yemabhodhoro egirazi
kuti solifenacin succinate inonyanya kuchengetwa mumhinduro.Tafura 4 nhamba
Zvave zvichiratidzwa kuti kana solifenacin succinate yakachengetwa mubhodhoro regirazi, shandisa
Mushure meiyo organic solvent mhinduro yemuenzaniso wepamusoro yakanyungudutswa, iyo succinate mumidziyo yegirazi.Nzvimbo yepamusoro yelinacin mukati me48h yakafanana nenzvimbo yepamusoro yePP vial pa0h.Pakati pe0.98 ne1.02, iyo data yakagadzikana.
3.0 mhedziso:
Mhando dzakasiyana dzemabhodhoro egirazi kune isina simba base compound succinic acid Solifenacin inoburitsa madhigirii akasiyana eadsorption, iyo adsorption inonyanya kukonzerwa nekudyidzana kweprotonated amine mapoka ane emahara silanol mapoka.Naizvozvo, chinyorwa ichi chinoyeuchidza makambani ekuyedza zvinodhaka kuti panguva yekuchengetera mvura kana kuongororwa, ive shuwa yekuteerera kurasikirwa kwemushonga, yakakodzera diluent pH kana yakakodzera diluent pH inogona kuongororwa pachine nguva.Muenzaniso saka kune oganic zvinonyungudutsa kudzivirira kusangana pakati pemishonga yakakosha negirazi, kuitira kuderedza kusarura kwedata panguva yekuongorora zvinodhaka uye mhedzisiro inokonzeresa pakuferefeta.
[1] Nema S, Ludwig JD.Pharmaceutical dosage mafomu - parenteral mishonga: vhoriyamu 3: mirairo, kusimbiswa uye ramangwana.3rd ed.Crc Press;2011.
[2] https://go.drugbank.com/drugs/DB01591
[3] El-Shamy TM.Kusimba kwemakemikari eK2O-CaO-MgO-SiO2 magirazi, Phys Chem Glass 1973;14:1-5.
[4] El-Shamy TM.Iyo nhanho-yekutarisa nhanho mukugadzirisa kwesilicateglasses.
Phys Chem Glass 1973;14:18-19.
[5] Mathes J, Friess W. Kufurira kwepH uye ionic simba paIgG adsorption tovials.
Eur J Pharm Biopharm 2011, 78(2):239-
[6] Bacon FR, Raggon FC.Kusimudzirwa kweKurwisa Girazi neSilica neCitrateand
Mamwe Anions muNeutral Solution.J AM
Mufananidzo 4. Kudyidzana pakati peboka reprotonated amino re solifenacin uye mapoka e-silanol akaparadzaniswa pamusoro pegirazi pamusoro.
Nguva yekutumira: May-26-2022