Umwanditsi / 1,2 Hu Rong 1 Hol ingoma Ingoma Indirimbo Xuezhi mbere yuruzinduko 1 Jinsong 1 - Agashya 1, 2
【Abstract glass Ikirahuri cya Borosilike ni ibikoresho bikoreshwa mu gupakira no gukemura ibibazo mu nganda zimiti.Nubwo ifite ibimenyetso biranga imbaraga nyinshi, nko kurwanya neza, kwangirika no kwangirika, kwambara ibyuma hamwe nitsinda rya silanol bikubiye mubirahuri bya borosilike birashobora gukorana nibiyobyabwenge.Mu isesengura ryimiti yimiti ikoresheje chromatografiya ikora cyane (HPLC), isahani isanzwe yo gutera ni ikirahuri cya borosilike.Mu gukora iperereza ku ngaruka ziterwa n’ibirahuri bya HPLC by’ibirango bitatu ku ituze rya solifenacin succincate ikaba ari uruganda rwa alkaline idakomeye, byagaragaye ko kwinjiza imiti ya alkaline yabayeho mu bikoresho by’ibirahure byakozwe n’abakora inganda zitandukanye.Adorption yatewe ahanini nubusabane bwa amino protonated amino na dissociative group ya silanol, kandi kuba succincate yarayitezimbere.Kwiyongera kwa hydrochloric aside bishobora kwangiza imiti cyangwa kongeramo igipimo gikwiye cyumuti wumuti bishobora kwirinda adsorption.Intego yuru rupapuro ni ukwibutsa ibigo bipima ibiyobyabwenge kwitondera imikoranire hagati yibiyobyabwenge bya alkaline nikirahure, no kugabanya gutandukana kwamakuru hamwe niperereza ryitandukanyirizo ryatewe no kubura ubumenyi bwimiterere ya adsorption iranga amacupa yikirahure muri inzira yo gusesengura ibiyobyabwenge.
Amagambo shingiro: Solifenacin succinc, itsinda rya amino, ibirahuri bya HPLC, adsorb
Ikirahure nkibikoresho byo gupakira bifite ibyiza byo koroha, kurandura byoroshye no kurwanya ruswa. Kwangirika, kwambara birwanya, guhagarara kwinshi nibindi byiza, bityo bikoreshwa cyane mugukoresha imiti.Ikirahuri cyimiti kigabanijwemo sodium calcium ikirahuri na borosilicate ikirahure, ukurikije ibice bitandukanye birimo.Muri byo, ikirahuri cya soda kirimo 71% ~ 75% SiO2, 12% ~ 15% Na2O, 10% ~ 15% CaO;ikirahuri cya borosilike kirimo 70% ~ 80% SiO2, 7% ~ 13% B2O3, 4% ~ 6% Na2O na K2O na 2% ~ 4% Al2O3.Ikirahuri cya Borosilicate gifite imiti irwanya imiti bitewe no gukoresha B2O3 aho gukoresha Na2O na CaO
Kubera imiterere yubumenyi, yatoranijwe nkigikoresho nyamukuru cyubuvuzi bwamazi.Nyamara, ikirahuri cya boronSilicone, nubwo irwanya cyane, irashobora gukomeza gukorana nibiyobyabwenge, Hariho uburyo bune busanzwe bwo kwitwara kuburyo bukurikira [1]:
1) Guhana Ion: Na +, K +, Ba2 +, Ca2 + mu kirahure bahura na ion hamwe na H3O + inthe igisubizo, kandi hariho reaction hagati ya ion zahinduwe nibiyobyabwenge;
)na Al3 + irekurwa mubisubizo;
3) Ruswa: EDTA iboneka mugisubizo cyibiyobyabwenge (EDTA) irashobora kugorana hamwe na ion zingana cyangwa ion zingana mubirahure
4) Adsorption: Hariho umurongo wa Si-O wacitse hejuru yikirahure, gishobora kwamamaza H +
Ihinduka rya OH- rishobora gukora hydrogène ihuza amatsinda amwe mumiti, bikavamo ibiyobyabwenge byerekanwa hejuru yikirahure.
Imiti myinshi irimo amine yibanze ya amine, Iyo usesenguye imiti yimiti hamwe na chromatografiya ikora cyane (HPLC), vial ikoreshwa cyane ya HPLC autosampler ikozwe mubirahuri bya borosilike, kandi kuba SiO- hejuru yikirahure bizahuza nitsinda rya amine protonone , kwemerera ubucucike bwibiyobyabwenge kugabanuka, ibisubizo byisesengura bizaba bidahwitse, na laboratoire OOS (Out of Specification).Muri iyi raporo, intege nke zifatizo (pKa ni 8.88 [2]) ibiyobyabwenge bya solifenacin (formulaire yuburyo bwerekanwa ku gishushanyo 1) bikoreshwa nkibikoresho byubushakashatsi, kandi ingaruka ziterwa n’ibikoresho byinshi byo guteramo ibirahuri bya amber borosilike ku isoko ku isesengura ry’ibiyobyabwenge ni iperereza., kandi duhereye kubisesengura kugirango tubone igisubizo cya adsorption yibiyobyabwenge nkibi birahure.
1.Ikizamini
1.1 Ibikoresho nibikoresho byo kugerageza
1.1.1 Ibikoresho: Agilent Gukora neza hamwe na UV Detector
Amazi ya chromatografiya
1.1.2 Ibikoresho byubushakashatsi: Solifenacin succinate API yakozwe na Alembic
Pharmaceuticals Ltd (Ubuhinde).Igipimo cya Solifenacin (99,9% cyera) cyaguzwe muri USP.ARgrade potassium dihydrogen fosifate, triethylamine, na acide fosifori yaguzwe mu Bushinwa Xilong Technology Co., Ltd. , na 2ml amber amacupa yikirahure HPLC yaguzwe muri Agilent Technologies (Ubushinwa) Co, Ltd., Dongguan Pubiao Laboratory Equipment Technology Co., Ltd., na Zhejiang Hamag Technology Co., Ltd. (A, B, C bikoreshwa hepfo guhagararira amasoko atandukanye yibirahuri, kimwe).
1.2HPLC uburyo bwo gusesengura
1.2.1.Hamwe na fosifate ya fosifate (ipima g 4.1 g ya potasiyumu dihydrogen fosifate, ipima ml 2 ya triethylamine, iyongereho kuri 1 L y'amazi ya ultrapure, ukangure gushonga, aside usephosifike (pH yahinduwe kuri 2.5) -acetonitrile-methanol (40:30:30) nk'icyiciro kigendanwa,
Igishushanyo 1 Imiterere yuburyo bwa solifenacin succinc
Igishushanyo cya 2 Kugereranya ahantu h'imisozi yumuti umwe wa solifenacine ihurira mumashanyarazi ya PP hamwe nikirahure cyibirahure biva mubakora batatu A, B, na C
ubushyuhe bwinkingi bwari 30 ° C, umuvuduko wamazi wari 1.0 mL / min, naho inshinge zatewe ni 50 mL, Uburebure bwumurongo ni 220 nm.
1.2.2. igipimo 1.0 mL / min, ubushyuhe bwinkingi 55 ° C, nubunini bwatewe ni 90 mL.Chromatogramu yabonetse kuri 204 nm.
1.3 Uburyo bwo gusesengura ICP-MS
Ibintu byakemuwe byasesenguwe hakoreshejwe sisitemu ya Agilent 7800 ICP-MS, uburyo bwo gusesengura yari He mode (4.3mL / min), ingufu za RF yari 1550W, igipimo cya gaze ya plasma cyari 15L / min, naho umuvuduko wa gazi itwara yari 1.07mL / min.Ubushyuhe bwicyumba cyubushyuhe bwa 2 ° C, umuvuduko wo guterura pompe ya peristaltike ni 0.3 / 0.1 rps, icyitegererezo cyo guhagarara cyari 35 s, igihe cyo guterura icyitegererezo cyari 45 s, naho ubujyakuzimu bwa mm 8.
Icyitegererezo
Solifenacin succinate igisubizo: yateguwe namazi ya ultrapure, theconcentration ni 0.011 mg / mL.
1.4.2 Acide acide acide: yateguwe namazi ya ultrapure, intumbero ni 1mg / mL.
1.4.Ethyl acetate layer yahise itandukana hanyuma thesolvent ihumeka kugirango itange solifenacin.Kunyunyuza urugero rukwiye rwa solifenacin inethanol (Ethanol ihwanye na m 5% mugisubizo cyanyuma), hanyuma ukayungurura amazi kugirango utegure igisubizo hamwe na 0.008 mg / mL solifenacin (hamwe numuti wa solifenacin succincate uri mubisubizo kimwe na solifenacin kwibanda).
Ibisubizo n'ibiganiro
·····················. ··
2.1 Ubushobozi bwa Adsorption yububiko bwa HPLC bwibirango bitandukanye
Tanga igisubizo kimwe cyamazi ya solifenacin ihindurwe mumashanyarazi ya PP kandi ibirango 3 byamavuta ya autosampler yatewe mugihe kimwe mubidukikije, kandi agace k'impinga ya mpinga nkuru karanditswe.Duhereye ku bisubizo biri mu gishushanyo cya 2, birashobora kuba bigaragara ko impinga yimisozi ya PP itajegajega, kandi nta mpinduka ihari nyuma ya 44 h.Mu gihe uduce twinshi twibirango bitatu byibirahure byibirahure kuri 0 h byari bito kurenza icupa rya PP , kandi agace ka mpinga gakomeje kugabanuka mugihe cyo kubika.
Igicapo ca 3
Kugirango urusheho kwiga kuri iki kintu, solifenacin, aside irike, ibisubizo byamazi ya acide solifenacine hamwe na succinc mubirahuri byibirahure byabacupa band PP amacupa kugirango bakore iperereza kumihindagurikire yikibanza hamwe nigihe, kandi icyarimwe ikirahure
Ibisubizo bitatu mubibindi byahujwe no gukoresha Agilent 7800 ICP-MSPlasma mass spectrometer kugirango isesengure ryibanze.Imibare iri ku gishushanyo cya 3 yerekana ko indanga ya Glass mu mazi yo mu mazi itigeze itanga adsorbide acide, ahubwo yashizwemo na solifenacinFree base na solifenacin.Ibirahuri by'ibirahuri adsorb bigenda neza.Ingano ya linacin irakomeye kuruta iya solifenacin yubusa, mugihe cyambereSolifenacin succinate na solifenacin yubusa mubibindi byikirahure.Ikigereranyo cyibice byibisubizo byibisubizo biri mumacupa ya PP byari 0,94 na 0,98.
Muri rusange abantu bemeza ko hejuru yikirahuri cya silikatike gishobora gukuramo amazi, ayo mazi amwe agahuza na Si4 + muburyo bwamatsinda ya OH kugirango agire amatsinda ya silanol Mugizwe nikirahure cya oxyde, ion polyvalent ntishobora kugenda, ariko ibyuma bya alkali (nka Na +) hamwe na alkaline yisi ibyuma (nka Ca2 +) birashobora kugenda mugihe ibintu byemewe, cyane cyane ion ya alkali ibyuma byoroshye byoroshye, birashobora guhanahana na H + byamamaza hejuru yikirahure hanyuma ugahindura hejuru yikirahure kugirango ugire amatsinda ya silanol [3-4].Kubwibyo, kwibanda kuri H + Kwiyongera gushobora guteza imbere ion guhana kugirango wongere amatsinda ya silanol hejuru yikirahure.kumeza1 yerekana ko ibikubiye muri B, Na, na Ca mubisubizo bitandukana kuva hejuru kugeza hasi.ni acide succinic, solifenacin succinate na solifenacin.
icyitegererezo B (μg / L) Na (μg / L) Ca (μg / L) Al (μg / L) Si (μg / L) Fe (μg / L)
amazi 2150 3260 20 Nta gutahura 1280 4520
Acide acide acide 3380 5570 400 429 1450 139720
Solifenacin Igisubizo Cyuzuye 2656 5130 380 Nta Kumenya 2250 2010
solifenacin igisubizo 1834 2860 200 Nta gutahura 2460 Nta gutahura
Imbonerahamwe 1 Ibintu byibanze bya solifenacin succinc, solifenacin na acide succinic acide amazi yabitswe mubibindi byibirahure muminsi 8
Byongeye kandi, birashobora kugaragara mubyatanzwe mu mbonerahamwe ya 2 ko nyuma yo kubika mumacupa yikirahure kumasaha 24 h, gushonga pH yamazi yazamutse.Iyi phenomenon yegereye cyane ibitekerezo byavuzwe haruguru
Vial Oya Igipimo cyo gukira nyuma yo kubika mubirahuri kuri 71 h
(%) Igipimo cyo gukira nyuma ya PH ihinduwe
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
Imbonerahamwe 3 Imiterere ya desorption ya solifenacin irasimburana nyuma yo kongeramo aside
Kubera ko Si-OH hejuru yikirahure ishobora gutandukanywa muri SiO- [5] hagati ya pH 2 ~ 12, mugihe solifenacin ibaho N mubidukikije bya acide Protonation (yapimwe pH yumuti wamazi wa solifenacin succinc ni 5.34, pH agaciro ka solifenacin igisubizo ni 5.80), kandi itandukaniro riri hagati yimikoranire yombi ya Hydrophilique itera ibiyobyabwenge byinjira mubirahure (Ishusho 3), solifenacin yamamajwe cyane kandi mugihe runaka.
Byongeye kandi, Bacon na Raggon [6] basanze kandi mubisubizo bidafite aho bibogamiye, aside hydroxy hamwe nitsinda rya hydroxyl mumwanya ugereranije nitsinda rya carboxyl Itsinda ryumunyu rishobora gukuramo silisiyumu ya okiside.Mu miterere ya molekuline ya solifenacin succinc, hari itsinda rya hydroxyl ugereranije nu mwanya wa karubasi, izatera ku kirahure, SiO2 ikuramo kandi ikirahure kirashonga.Kubwibyo, nyuma yumunyu hamwe na acide succinic, adsorption ya solifenacine mumazi iragaragara cyane.
2.2 Uburyo bwo kwirinda adsorption
Igihe cyo kubika pH
0h 5.50
24h 6.29
48h 6.24
Imbonerahamwe 2 pH ihinduka ryibisubizo byamazi ya solifenacin ihindagurika mumacupa yikirahure
Nubwo ibibindi bya PP bidatanga adsorb solifenacin bigenda bisimburana, Ariko mugihe cyo kubika igisubizo muri vial ya PP, havuka izindi mpinga zanduye kandi Kongera igihe cyo kubika bigenda byongera buhoro buhoro agace k’umwanda, ibyo bikaba byaratumye habaho kwivanga mu kumenya impinga nkuru .
Kubwibyo, birakenewe gushakisha uburyo bushobora gukumira ibirahuri.
Fata 1.5 mL ya solifenacin succinate igisubizo cyamazi mumashanyarazi.Nyuma yo gushyirwa mubisubizo kuri 71 h, igipimo cyo gukira cyari gito.Ongeramo aside 0.1M hydrochloric, hindura pH kuri 2,3, uhereye kumibare iri mumeza 3. Birashobora kugaragara ko igipimo cyo gukira cyose cyagarutse kurwego rusanzwe, byerekana ko reaction ya adsorption storagetime ishobora guhagarikwa kuri pH yo hepfo.
Ubundi buryo nukugabanya adsorption wongeyeho ibishishwa kama.Kora 10%, 20%, 30%, 50% methanol, Ethanol, isopropanol, acetonitrile yateguwe ku gipimo cya 0.01 mg / mL mumazi ya Solifenacin.Ibisubizo byavuzwe haruguru byashyizwe mubibindi byikirahure na vial PP.Ku bushyuhe bwicyumba Igihagararo cyacyo cyizwe cyerekana.Iperereza ryerekanye ko ibishishwa bike cyane bidashobora gukumira adsorption, mugihe ibishishwa kama cyane bishobora gutuma habaho imiterere idasanzwe yimisozi miremire bitewe ningaruka zo gukemura.Gusa ibishishwa byingirakamaro birashobora kongerwaho kugirango birinde neza aside irike Solifenacin yandikwa ku kirahure, ongeramo 50% methanol cyangwa Ethanol cyangwa 30% ~ 50% acetonitrile irashobora gutsinda imikoranire idahwitse hagati yibiyobyabwenge nubuso bwa vial.
Ibibindi bya PP Ibirahure Ibirahure Ibirahure Ibirahure
Igihe cyo kubika 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
Imbonerahamwe 4 Ingaruka zumuti utandukanye kama kuri adsorption yamacupa yikirahure
ko solifenacin succinate ikunzwe kugumana igisubizo.Imbonerahamwe 4
Byerekanwe ko iyo solifenacin succinc ibitswe mubibindi byikirahure, koresha
Nyuma yumuti wibisubizo byurugero rwavuzwe haruguru bigabanijwe, succinc mumashanyarazi.Ubuso bwa linacin muri 48h ni kimwe nubuso bwa PP vial kuri 0h.Hagati ya 0,98 na 1.02, amakuru arahamye.
3.0 umwanzuro:
Ibirango bitandukanye byibirahuri byibirahure bya acide succinic acide Solifenacin bizatanga impamyabumenyi zitandukanye za adsorption, adsorption iterwa ahanini nubusabane bwamatsinda ya amine protonone hamwe nitsinda rya silanol yubusa.Kubwibyo, iyi ngingo iributsa ibigo bipima ibiyobyabwenge ko mugihe cyo kubika amazi cyangwa gusesengura, menya neza ko witaye ku gutakaza ibiyobyabwenge, pH ikwiye cyangwa pH ikwiye irashobora gukorwaho iperereza hakiri kare.Urugero rero kumashanyarazi ya oganic kugirango yirinde imikoranire hagati yibiyobyabwenge byibanze nikirahure, kugirango bigabanye kubogama kwamakuru mugihe cyo gusesengura ibiyobyabwenge hamwe no kubogama kwiperereza.
[1] Nema S, Ludwig JD.Ifishi yimiti yimiti - imiti yababyeyi: umuzingo wa 3: amabwiriza, kwemeza nigihe kizaza.Icya gatatu.Itangazamakuru rya Crc; 2011.
[2] https://go.drugbank.com/ibiyobyabwenge/DB01591
El-Shamy TM.Imiti iramba ya K2O-CaO-MgO-SiO2, ibirahuri bya Chem Chem 1973;14: 1-5.
El-Shamy TM.Intambwe igena igipimo muri dealkalisation ya silicateglasses.
Ikirahure cya Chem Chem 1973;14: 18-19.
[5] Mathes J, Umufaransa W. Ingaruka za pH nimbaraga za ionic kuri IgG adsorption tovial.
Eur J Pharm Biopharm 2011, 78 (2): 239-
[6] Bacon FR, Raggon FC.Gutezimbere Igitero kuri Glass na Silica na Citrateand
Izindi Anion mugukemura kutabogamye.J AM
Igicapo 4. Imikoranire hagati ya amino protonate ya solifenacin na matsinda ya silanol yatandukanijwe hejuru yikirahure
Igihe cyoherejwe: Gicurasi-26-2022