Mawallafi / 1,2 Hu Rong 1 Hol drum Drum Song Xuezhi kafin yawon shakatawa 1 Jinsong 1 - Sabuwar 1, 2
【Abstract】 Borosilicate gilashin ne yadu amfani marufi abu da kuma bayani ganga a cikin Pharmaceutical masana'antu.Kodayake yana da sifofin juriya mai ƙarfi, kamar sumul, juriya na lalata da juriya, ions ƙarfe da ƙungiyoyin silanol waɗanda ke cikin gilashin borosilicate na iya har yanzu mu'amala da kwayoyi.A cikin nazarin magungunan sinadarai ta babban aikin ruwa chromatography (HPLC), vial na yau da kullun shine gilashin borosilicate.Ta hanyar binciken tasirin gilashin HPLC na nau'ikan nau'ikan nau'ikan iri uku akan kwanciyar hankali na solifenacin succinate wanda shine mahaɗan alkaline mai rauni, an gano cewa adsorption ga magungunan alkaline ya kasance a cikin gilashin gilashin da masana'antun daban-daban suka samar.Adsorption ya samo asali ne ta hanyar hulɗar protonated amino and dissociative silanol group, kuma kasancewar succinate ya inganta shi.Bugu da ƙari na hydrochloric acid zai iya lalata maganin ko ƙara daidai adadin abubuwan kaushi na kwayoyin halitta zai iya hana adsorption.Manufar wannan takarda ita ce tunatar da kamfanonin gwajin magunguna da su mai da hankali kan hulɗar da ke tsakanin magungunan alkaline da gilashi, da kuma rage karkatar da bayanai da aikin bincike na karkatar da aka samu sakamakon rashin sanin halayen tallan kwalabe a cikin gilashin gilashi. tsarin bincike na miyagun ƙwayoyi.
Mahimman kalmomi: Solifenacin succinate, rukunin amino, HPLC gilashin vials, adsorb
Gilashi a matsayin marufi yana da fa'idodi na santsi, sauƙin kawarwa da juriya na lalata.Lalata, juriya juriya, kwanciyar hankali ƙara da sauran fa'idodi, don haka ana amfani dashi sosai a cikin aikace-aikacen magunguna.Gilashin magani ya kasu kashi sodium calcium glass da gilashin borosilicate, bisa ga sassa daban-daban da ya ƙunshi.Daga cikin su, soda lemun tsami gilashin ya ƙunshi 71% ~ 75% SiO2, 12% ~ 15% Na2O, 10% ~ 15% CaO;gilashin borosilicate ya ƙunshi 70% ~ 80% SiO2, 7% ~ 13% B2O3, 4% ~ 6% Na2O da K2O da 2% ~ 4% Al2O3.Gilashin Borosilicate yana da kyakkyawan juriya na sinadarai saboda amfani da B2O3 maimakon mafi yawan Na2O da CaO.
Saboda yanayin kimiyya, an zaɓi shi a matsayin babban akwati don maganin ruwa.Duk da haka, gilashin boronSilicone, ko da tare da babban juriya, na iya har yanzu mu'amala da kwayoyi, Akwai hanyoyin amsawa guda huɗu kamar haka [1]:
1) Canjin ion: Na + , K+ , Ba2 +, Ca2 + a cikin gilashin yin musayar ion tare da H3O + a cikin bayani, kuma akwai amsa tsakanin ions da aka yi musayar da miyagun ƙwayoyi;
2) Gilashin rushewa: Phosphate, oxalate, Citrates da tartrates zasu hanzarta rushe gilashin kuma suna haifar da silicides.kuma an saki Al3+ cikin mafita;
3) Lalacewa: EDTA da ke cikin maganin miyagun ƙwayoyi (EDTA) na iya yin rikitarwa tare da ions divalent ko ions trivalent a cikin gilashin.
4) Adsorption: Akwai karya Si-O bond a kan gilashin surface, wanda zai iya adsorb H +
Samuwar OH- na iya samar da haɗin gwiwar hydrogen tare da wasu ƙungiyoyi a cikin miyagun ƙwayoyi, wanda ya haifar da ƙaddamar da miyagun ƙwayoyi zuwa saman gilashi.
Yawancin sinadarai sun ƙunshi ƙungiyoyin amine marasa ƙarfi, Lokacin da ake nazarin magungunan sinadarai tare da babban aikin ruwa chromatography (HPLC), vial ɗin da aka saba amfani da shi na HPLC autosampler wanda aka yi da gilashin borosilicate, da kasancewar SiO- akan saman gilashin zai yi hulɗa tare da rukunin amine mai haɓaka. , ƙyale yawan ƙwayar miyagun ƙwayoyi ya ragu, sakamakon binciken zai zama maras kyau, da kuma OOS na dakin gwaje-gwaje (Fita daga Ƙayyadaddun Ƙira).A cikin wannan rahoto, ana amfani da ƙarancin asali (pKa shine 8.88 [2]) solifenacin succinate (ana nuna tsarin tsarin a cikin Hoto 1) azaman abin bincike, da kuma tasirin allurar gilashin amber borosilicate da yawa akan kasuwa akan nazarin miyagun ƙwayoyi. ana bincike., kuma daga mahangar nazari don samun mafita ga tallan irin waɗannan kwayoyi akan gilashi.
1.Test part
1.1 Kayan aiki da kayan aiki don gwaji
1.1.1 Kayan aiki: Agilent Babban Haɓaka tare da Mai gano UV
Liquid chromatography
1.1.2 Kayan Gwaji: Solifenacin succinate API ne ya samar da Alembic
Pharmaceuticals Ltd. (Indiya).Ma'aunin Solifenacin (99.9% tsafta) an saya daga USP.ARgrade potassium dihydrogen phosphate, triethylamine, da phosphoric acid da aka saya daga China Xilong Technology Co., Ltd. Methanol da acetonitrile (duka HPLC grade) da aka saya daga Sibaiquan Chemical Co., Ltd. Polypropylene (PP) kwalabe da aka saya daga ThermoScientific (US) , da 2ml amber HPLC gilashin kwalabe da aka saya daga Agilent Technologies (China) Co., Ltd., Dongguan Pubiao Laboratory Equipment Technology Co., Ltd., da Zhejiang Hamag Technology Co., Ltd. (A, B, C ana amfani da su a kasa). don wakiltar tushen daban-daban na gilashin gilashi, bi da bi).
Hanyar bincike ta 1.2HPLC
1.2.1Solifenacin succinate da solifenacin kyauta tushe: chromatographic shafi isphenomenex luna®C18 (2), 4.6 mm × 100 mm, 3 µm.Tare da buffer phosphate (nauyin 4.1 g na potassium dihydrogen phosphate, auna 2 ml na triethylamine, ƙara shi zuwa 1 L na ruwa ultrapure, motsawa don narkewa, amfaniphosphoric acid (pH an daidaita zuwa 2.5) -acetonitrile-methanol (40:30:30) a matsayin tsarin wayar hannu,
Hoto 1 Tsarin tsari na solifenacin succinate
Hoto 2 Kwatanta wuraren kololuwar wannan maganin solifenacin succinate a cikin filayen PP da gilashin gilashi daga masana'antun A, B, da C guda uku.
zafin jiki na ginshiƙi ya kasance 30 ° C, ƙimar kwarara ya kasance 1.0 ml / min, kuma ƙarar allurar shine 50 ml, Tsawon tsayin ganowa shine 220 nm.
1.2.2 Succinic acid samfurin: ta amfani da YMC-PACK ODS-A 4.6 mm × 150 mm, 3 µm shafi, 0.03 mol / L phosphate buffer (daidaita zuwa pH 3.2 tare da phosphoric acid) -methanol (92: 8) a matsayin wayar hannu lokaci, gudana adadin 1.0 ml/min, shafi zazzabi 55 °C, kuma ƙarar allurar shine 90 ml.An samo chromatograms a 204 nm.
1.3 Hanyar bincike ta ICP-MS
An bincika abubuwan da ke cikin maganin ta amfani da tsarin Agilent 7800 ICP-MS, yanayin bincike shine Yanayin Shi (4.3mL / min), ƙarfin RF shine 1550W, ƙimar gas ɗin plasma ya kasance 15L / min, kuma ƙimar iskar gas mai ɗaukar nauyi. 1.07ml/min.Yanayin dakin hazo ya kasance 2 ° C, saurin haɓakawa / daidaitawa na peristaltic shine 0.3 / 0.1 rps, lokacin daidaitawar samfurin shine 35 s, lokacin ɗaukar samfurin shine 45 s, kuma zurfin tarin shine 8 mm.
Samfurin shiri
Solifenacin succinate bayani: shirya tare da ultrapure ruwa, maida hankali ne 0.011 MG / ml.
1.4.2 Succinic acid bayani: an shirya shi da ruwa mai ƙarfi, maida hankali shine 1mg/mL.
1.4.3 Maganin Solifenacin: narkar da solifenacin succinate a cikin ruwa, an ƙara sodium carbonate, kuma bayan an canza maganin daga farin tomilky mara launi, an ƙara ethyl acetate.An raba Layer acetate na ethyl kuma an kwashe daskararre don ba da solifenacin.Narkar da adadin da ya dace na solifenacin inethanol (ethanol yana lissafin m 5% a cikin bayani na ƙarshe), sannan a tsoma shi da ruwa don shirya maganin tare da maida hankali na 0.008 MG / ml solifenacin (tare da maganin solifenacin succinate wanda ke cikin maganin daidai da solifenacin). maida hankali).
Sakamako da Tattaunawa
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2.1 Adsorption na HPLC vials na iri daban-daban
Bayar da maganin ruwa iri ɗaya na solifenacin succinate cikin PP vials kuma an yi allurar nau'ikan nau'ikan autosampler guda 3 a lokaci guda a cikin mahalli guda, kuma an yi rikodin kololuwar yanki na babban kololuwar.Daga sakamakon da aka samu a cikin Hoto 2, ana iya ganin cewa mafi girman yanki na PP vials yana da kwanciyar hankali, kuma kusan babu wani canji bayan 44 h. Yayin da ƙananan wurare na nau'i uku na gilashin gilashin gilashi a 0 h sun kasance ƙasa da kwalban PP. , kuma mafi girman yanki yana ci gaba da raguwa yayin ajiya.
Hoto 3 Canje-canje a cikin kololuwar wuraren solifenacin, succinic acid, da solifenacin succinate mafitacin ruwa da aka adana a cikin filayen gilashi da filayen PP.
Don kara nazarin wannan sabon abu, solifenacin, succinate acid, ruwa mai ruwa mafita na solifenacin acid da succinate a cikin gilashin vials na manufacturer Band PP kwalabe don bincikar canji na kololuwa yanki tare da lokaci, kuma a lokaci guda gilashin.
Magani guda uku a cikin vials an haɗa su ta hanyar amfani da Agilent 7800 ICP-MSPlasma mass spectrometer don bincike na farko.Bayanan da ke cikin Hoto na 3 sun nuna cewa a cikin gilashin gilasai a cikin matsakaiciyar ruwa ba su shayar da succinic acid ba, amma sun tallata tushen solifenacinFree da solifenacin succinate.Gilashin gilashin suna ɗaukar succinate.Girman linacin ya fi ƙarfi fiye da na tushen kyauta na solifenacin, a farkon lokacin Solifenacin succinate da tushen kyauta na solifenacin a cikin gilashin gilashi.Matsakaicin wuraren kololuwar mafita da ke cikin kwalabe na PP sune 0.94 da 0.98, bi da bi.
An yi imani da cewa saman gilashin silicate zai iya sha ruwa, wanda wasu ruwa ya haɗu da Si4 + a cikin nau'i na kungiyoyin OH don samar da ƙungiyoyin silanol A cikin abun da ke cikin gilashin oxide, ions polyvalent ba zai iya motsawa ba, amma alkali karfe (kamar su). Na + ) da alkaline earth karfe ions (kamar Ca2+) na iya motsawa lokacin da yanayi ya ba da izini, musamman ma ions ƙarfe na alkali suna da sauƙin kwarara, suna iya musanya tare da H + da aka sanya akan gilashin gilashi kuma Canja wurin gilashin gilashi don samar da ƙungiyoyin silanol [3-4].Sabili da haka, ƙaddamarwar H + na karuwa zai iya inganta musayar ion don ƙara ƙungiyoyin silanol akan gilashin gilashi.ta tebur1 yana nuna cewa abun ciki na B, Na, da Ca a cikin maganin ya bambanta daga babba zuwa ƙasa.Succinic acid, solifenacin succinate da solifenacin.
samfurin B (μg/L) Na (μg/L) Ca (μg/L) Al (μg/L) Si (μg/L) Fe (μg/L)
ruwa 2150 3260 20 Babu Ganewa 1280 4520
Maganin Succinic acid 3380 5570 400 429 1450 139720
Solifenacin Succinate Magani 2656 5130 380 Babu Ganewa 2250 2010
Maganin solifenacin 1834 2860 200 Babu Ganewa 2460 Babu Ganewa
Tebur 1 Abubuwan da aka tattara na solifenacin succinate, solifenacin da succinic acid maganin ruwa da aka adana a cikin gilashin gilashin na kwanaki 8
Bugu da ƙari, ana iya gani daga bayanan da ke cikin Table 2 cewa bayan ajiya a cikin kwalabe na gilashi don 24 h, narkar da pH na ruwa ya tashi.Wannan lamari yana kusa da ka'idar da ke sama
Vial No. Adadin farfadowa bayan ajiya a gilashin don 71 h
(%) Adadin farfadowa bayan an daidaita PH
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
Tebur 3 Yanayin lalata na solifenacin succinate bayan ƙara acid
Tun da Si-OH akan fuskar gilashin za'a iya raba shi cikin SiO-[5] tsakanin pH 2 ~ 12, yayin da solifenacin ke faruwa N a cikin yanayin acidic Protonation (auna pH na maganin ruwa na solifenacin succinate shine 5.34, ƙimar pH na solifenacin). bayani shine 5.80), kuma bambanci tsakanin hulɗar Hydrophilic guda biyu yana haifar da tallan miyagun ƙwayoyi a kan gilashin gilashi (Fig. 3), an ƙara solifenacin fiye da lokaci.
Bugu da ƙari, Bacon da Raggon [6] kuma sun gano cewa a cikin bayani mai tsaka-tsaki, acid hydroxy acid tare da ƙungiyar hydroxyl a matsayi dangane da ƙungiyar carboxyl Salt mafita na iya cire oxidized silicion.A cikin tsarin kwayoyin halitta na solifenacin succinate, akwai ƙungiyar hydroxyl dangane da matsayi na carboxylate, wanda zai kai hari kan gilashin, an cire SiO2 kuma gilashin ya lalace.Saboda haka, bayan samuwar gishiri tare da acid succinic, adsorption na solifenacin a cikin ruwa ya fi bayyana.
2.2 Hanyoyi don guje wa talla
Lokacin ajiya pH
0h 5.50
24h 6:29
48h 6:24
Tebur 2 pH canje-canje na maganin ruwa na solifenacin succinate a cikin kwalabe na gilashi
Ko da yake PP vials ba sa adsorb solifenacin succinate, Amma a lokacin ajiya na bayani a cikin PP vial, wasu ƙazanta kololuwa suna haifar da Tsawanta lokacin ajiya a hankali ƙara ƙazanta kololuwar yankin, wanda ya haifar da tsangwama ga gano babban kololuwa. .
Sabili da haka, ya zama dole don gano hanyar da za ta iya hana tallan gilashi.
Ɗauki 1.5 ml na solifenacin succinate aqueous bayani a cikin gilashin gilashi.Bayan an sanya shi a cikin bayani don sa'o'i 71, adadin dawowa ya kasance ƙananan.Ƙara 0.1M hydrochloric acid, daidaita pH zuwa kimanin 2.3, daga bayanan da ke cikin Tebura 3. Ana iya ganin cewa adadin dawo da duk sun koma matakan al'ada, yana nuna cewa za a iya hana adsorption lokacin ajiyar ajiya a ƙananan pH.
Wata hanya ita ce rage adsorption ta hanyar ƙara abubuwan da ake amfani da su.Yi 10%, 20%, 30%, 50% methanol, ethanol, isopropanol, acetonitrile an shirya shi a wani taro na 0.01 mg/mL a cikin Solifenacin succinate ruwa.Abubuwan da ke sama an saka su a cikin gilashin gilashi da PP vials, bi da bi.A dakin da zafin jiki An yi nazarin kwanciyar hankali ya nuna.Binciken ya gano cewa ƙananan kaushi na kwayoyin halitta ba zai iya hana adsorption ba, yayin da sauran kaushi mai yawa zai haifar da mummunan siffar babban kololuwa saboda tasirin ƙarfi.Matsakaicin kaushi na halitta kawai za'a iya ƙara don hana succinic acid yadda yakamata Solifenacin an tallata shi akan gilashi, ƙara 50% methanol ko ethanol ko 30% ~ 50% acetonitrile na iya shawo kan raunin hulɗar tsakanin miyagun ƙwayoyi da saman vial.
Filayen PP Gilashin Gilashin Gilashin Gilashin Gilashin Gilashin Gilashin Gilashin Gilashin Gilashin
Lokacin ajiya 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
Table 4 Tasirin nau'ikan kaushi na kwayoyin halitta daban-daban akan tallan kwalabe na gilashi
cewa solifenacin succinate an fi son kiyaye shi a cikin bayani.Tebur 4 lambobi
An nuna cewa lokacin da aka adana solifenacin succinate a cikin gilashin gilashi, yi amfani da shi
Bayan da kwayoyin kaushi bayani na sama misali ne diluted, da succinate a cikin gilashin vials.Mafi girman yanki na linacin a cikin sa'o'i 48 daidai yake da mafi girman yanki na PP vial a 0h.Tsakanin 0.98 da 1.02, bayanan sun tabbata.
3.0 na ƙarshe:
Daban-daban nau'ikan gilashin gilashin don raunin tushe succinic acid Solifenacin zai samar da nau'ikan talla daban-daban, tallan tallan yana faruwa ne ta hanyar hulɗar ƙungiyoyin amine masu haɓakawa tare da ƙungiyoyin silanol kyauta.Sabili da haka, wannan labarin yana tunatar da kamfanonin gwajin magunguna cewa yayin ajiyar ruwa ko bincike, tabbatar da kula da asarar miyagun ƙwayoyi, za'a iya bincika pH mai dacewa da ya dace ko pH mai dacewa a gaba.Misali don maganin oganic don guje wa hulɗar da ke tsakanin magunguna na asali da gilashi, don rage ra'ayi na bayanai yayin nazarin miyagun ƙwayoyi da kuma sakamakon da aka samu akan bincike.
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[2] https://go.drugbank.com/drugs/DB01591
[3] El-Shamy TM.Darewar sinadaran K2O-CaO-MgO-SiO2 gilashin, Phys Chem Glass 1973;14:1-5.
[4] El-Shamy TM.Matakan ƙayyadaddun ƙimar a cikin ma'amalar silicateglasses.
Phys Chem Glass 1973;14: 18-19.
[5] Mathes J, Friess W. Tasirin pH da ƙarfin ionic akan tovials adsorption IgG.
Eur J Pharm Biopharm 2011, 78 (2): 239-
[6] Bacon FR, Raggon FC.Haɓaka harin Gilashin da Silica ta Citrateand
Sauran Anions a Magani Neutral.J AM
Hoto 4. Haɗin kai tsakanin rukunin amino protonated na solifenacin da ƙungiyoyin silanol da aka raba akan farfajiyar gilashi.
Lokacin aikawa: Mayu-26-2022