Musiyano uripo pakati peL-Cysteine ??Hydrochloride uye Anhydrous Substances: Ongororo Yakarongeka kubva kuMolecular Structure kuenda kuIndustrial Applications.
L-cysteine ????hydrochloride, seyakakosha kubva kune bioactive mamorekuru, ine yakafara mashandisirwo muminda yezvekudya, mishonga uye zvizorwa. Zvigadzirwa zvayo zvekutengesa zvinonyanya kuvepo mumhando mbiri - monohydrate ine crystalline mvura uye anhydrous isina crystalline mvura. Kunyange zvazvo mafomu maviri aya achibva kumakemikari akafanana, anoratidza misiyano yakakura nekuda kwekuvapo kana kusavapo kwemvura ine crystalline. Ichi chinyorwa chinotanga kubva kune akakosha makemikari zvivakwa uye nekuongorora zvakadzama mutsauko uripo pakati pezviviri izvi maererano nemuviri uye makemikari zvivakwa, kushanda kwemaindasitiri uye hupfumi hwehunyanzvi, zvichipa mareferensi esainzi ekutsvagisa nekusimudzira, kugadzira uye kushandisa mundima dzine hukama.
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I. Chemical Nature uye Structural Characteristics
1.1 Misiyano chaiyo mukuumbwa kwema molecular
Mushonga wemakemikari weL-cysteine ??hydrochloride monohydrate ndeye C?H?NO?S·HCl·H?O. Muchimiro chayo chekristaro, imwe neimwe molecule yeL-cysteine ????hydrochloride inosungirirwa kune imwe molecule yemvura kuburikidza nehydrogen bond. Mhando iyi yemamorekuru emvura haipo zvakasununguka asi yakamisikidzwa semvura ine crystalline panzvimbo dzakatarwa muretisi, ichigadzira chimiro chekubatanidza chakagadzikana. Kusiyana neizvi, chimiro chemakemikari yeanhydrous fomu inorerutswa kuC?H?NO?S·HCl, uye makristasi ayo anorongedzerwa zvakananga kuburikidza neiyo ionic bond uye intermolecular masimba, isina kuvakwa kwelattice kunosanganisira mamorekuru emvura.
1.2 Hunhu uye Kufananidza kweCrystal Zvimiro
X-ray diffraction analysis inoratidza kuti monohydrate crystal ndeye monoclinic crystal system, ine nzvimbo yeboka reP2?. The unit cell parameters is a=7.42 A, b=6.85 A, c=10.39 A, uye β=98.5°. Kuunzwa kwemamorekuru emvura kunowedzera iyo unit cell volume neanosvika 12%, ichigadzira yakavhurika sisitimu chimiro. Nekudaro, makristasi eanhydrous anoratidza imwe compact packing modhi, uye iwo diffraction mapatani anoratidza hunhu hwepamusoro pa2θ = 15.6 ° uye 24.3 °. Iyi misiyano inobata zvakananga maitiro emuviri ezviviri.
1.3 Tsigiro kubva kune theoretical kuverenga
Density functional theory (DFT) kuverenga kunoratidza kuti simba rinosunga remamorekuru emvura uye chikamu chehydrochloride mumonohydrate chinenge -28.6 kJ/mol. Uku kupindirana kwepakati-kusimba hakungovimbisi kugadzikana kwekristaro chete asiwo kunobvumira mamorekuru emvura kuti adzorerwe pasi pemamiriro ezvinhu chaiwo (sekupisa kusvika ku110 ℃). Iyo lattice simba reanhydrous crystals inosvika 7% yakakwirira kupfuura iyo yemonohydrate crystals, iyo inotsanangura yavo yepamusoro yekunyungudika asi hurombo hunyoro hwekunyura kugadzikana.
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Ii. Misiyano yakarongeka mune zvemuviri uye zvemakemikari zvinhu
2.1 Kupatsanurwa kwemaitiro e thermodynamic
Differential scanning calorimetry (DSC) bvunzo dzakaratidza kuti monohydrate yakanyunguduka yakanyunguduka pa 175-178 ° C, ichiperekedzwa ne endothermic peak (ΔH≈142 J/g), panguva iyo desorption yecrystalline mvura uye kuparara kwema molecular kwakaitika panguva imwe chete. Nekuda kwekushaikwa kwemvura ine crystalline, tembiricha yekuora yezvinhu anhydrous inowedzera kusvika 195-200 ℃, asi decomposition enthalpy shanduko inodzikira kusvika 118 J/g. Musiyano uyu unoratidza kuti zvinhu zveanhydrous zvinogona kunge zvine zvakanakira mukupisa-kupisa kwekushandisa mamiriro, asi hwindo rakatetepa rekugadzikana rinoda kunyatso kudzora.
2.2 Kuenzanisa kwekuparara kinetics
The dissolution kuedza mumvura pa 25 ℃ inoratidza kuti zvinongotora 45 seconds kuti monohydrate isvike kune yakazara concentration (inenge 1.2 mol / L), uye solubility kupisa i -15.2 kJ / mol. Zvisinei, iyo anhydrous substance inotora 120 seconds kuti isvike pakusangana kwakafanana, uye kupisa kwekuparara -19.8 kJ / mol. Iyi kinetic kusiyana kunobva pakuti pre-yakachengetwa hydrogen bond network mu monohydrate inonyanya kupindirana nemamorekuru emvura inonyungudutsa, iyo inonyanya kukosha pakugadzirwa kwejekiseni yemishonga inoda kukurumidza kupera.
2.3 Quantitative Ongororo ye mwando Absorption maitiro
Iyo dynamic mwando adsorption (DVS) bvunzo yakaratidza musiyano wakakosha: Pasi pemamiriro e25 ℃ uye 75% RH, huremu hwekunyudza huremu hwemonohydrate mukati memaawa makumi mana nemasere yaingova 0.8%, iyo yaienderana neiyo pharmacopoeia. Pasi pemamiriro akafanana, iyo anhydrous substance inowana 5.3% muhuremu mukati meawa matanhatu uye inoshandurwa zvachose kuita monohydrate mushure memaawa makumi maviri nemana. Ichi chimiro chinotarisa kuti anhydrous zvinhu zvinofanirwa kuve vacuum-yakazara nealuminium-plastiki inoumbwa firimu uye inoshandiswa pakarepo mushure mekuvhurwa.
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Iii. Iyo Yakadzama Mechanism yekugadzikana uye Reactivity
3.1 Kusiyana kwemakemikari ekuderedza nzira
Iyo yakakurumidza kugadzikana bvunzo (40 ℃ / 75% RH) yakaratidza kuti iyo oxidation hafu yeupenyu yeboka retiol (-SH) mumonohydrate yaive mwedzi gumi nemasere, uye chinhu chikuru chekudzikisira chigadzirwa chaive cystine. Pasi pemamiriro ezvinhu akafanana, hafu yehupenyu hwezvinhu zveanhydrous inopfupiswa kusvika kumwedzi 9, uye zvimwe ne-zvigadzirwa zvakadai sehydrogen sulfide uye sulfurous acid inogadzirwa. Izvi zvinoratidza kuti mvura yecrystalline inodzivirira mapoka etiol anoshanda nekugadzira mabhondi ehydrogen, achinonotsa maitiro ekuita oxidation.
3.2 Kuratidzwa kwakakosha kweiyo solid-state reactivity
Mukubatana-kuya kuyedza kwemishonga, iyo monohydrate yaive yakanaka kuenderana ne magnesium stearate, uye hapana kuita kwakaonekwa mushure memazuva makumi matanhatu. Pasi pemamiriro akafanana, zvinhu zveanhydrous zvinosangana ne acid-base reaction ne magnesium stearate, zvichikonzera kudzikira kwemayunitsi 0.8 mupH. Musiyano uyu unoratidza kuti mukugadzirisa, kusarudzwa kwevabatsiri kunoda kufunga nezve hydration mamiriro eiyo inoshanda mishonga yemishonga.
3.3 Kuenzanisa Kudzidza paChiedza Kugadzikana
Iyo ultraviolet chiedza exposure test (4500Lx) yakaratidza kuti chiyero chekuchengetedza chemonohydrate solution (5%) chaiva> 95% mushure memaawa makumi maviri nemana, nepo anhydrous solution yakaratidza kuparara kwe10% mukati maawa gumi nemaviri. Zvinofungidzirwa kuti mvura yecrystalline inopa imwe nzira yekudzivirira chiedza nekudzima simba remamorekuru ehurumende anofara.
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Iv. Mapoinzi Akakosha eKugadzirwa Kweindasitiri uye Kudzora Kwemhando
4.1 Makiyi Paramita eiyo crystallization process
Kugadzirwa kwemaindasitiri emonohydrate kunotora nzira yekutonhodza yekristaro: nekudzora mwero wekutonhora we0.5 ℃/min, tembiricha yekupedzisira ye4 ℃, uye inomhanyisa kumhanya kwe120rpm, makristasi enguva dzose ane particle size yeD50=180μm anogona kuwanikwa. Anhydrous zvinhu zvinoda reverse solvent crystallization uchishandisa non-aqueous solvents (seanhydrous ethanol), iyo inowedzera kuoma kwemaitiro ne30% uye inoda kuchengetedzwa kwenitrogen kudzivirira kunyura.
4.2 Misiyano yemhando yekudzora zviyero
IEuropean Pharmacopoeia inotaura kuti hunyoro hwemonohydrate hunofanira kuva 7.5-9.5%, uye inosara pakupisa inofanira kuva ≤0.1%. Anhydrous zvinhu zvinoda mwando we ≤0.5%, asi muganhu wesimbi inorema wakaoma (≤5ppm vs ≤10ppm ye monohydrate). Uyu mutsauko wakajairika unoratidza mafomu akasiyana ezvingangoitika njodzi nzvimbo.
4.3 Zvinodiwa zvakakosha zvekuchengetedza uye zvekufambisa
Monohydrate inogona kuchengetwa munzvimbo inotonhorera (
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V. Scientific Selection Strategies yeApplication Scenarios
5.1 Mafungiro akasarudzika eindasitiri yeChikafu
Mukubika maapplication, monohydrate yave iyo mhedziso huru nekuda kwekukurumidza kunyungudika uye kuyerwa kuri nyore. Dhata kubva kune rimwe bhizinesi renyika dzakawanda rinoratidza kuti kushandiswa kwemonohydrate kunogona kuderedza kushandiswa kwesimba kune mukanyiwa unobvongodza ne15% uye kuwedzera huwandu hwechigadzirwa chakapedzwa ne8%. Chete mune yakanyanya-yakakwira shuga mukanyiwa (shuga yemukati> 30%), iyo yakaderera yekutanga mwando hunhu hweanhydrous zvinhu inogona kubatsira kunonoka kuita kweMaillard.
5.2 Muti weSarudzo mumunda weMishonga
Majekiseni anofanira kushandisa monohydrate (zvakajeka muUSP43-NF38); Mune oral solid dosage mafomu, kana iyo API inonzwa kunyorova (senge amoxicillin uye clavulanate potassium), kugona kweanhydrous zvinhu kunoda kuongororwa; Kugadzirira kwepamusoro kunogona kusarudzwa kusarudzwa, asi zvinofanira kuonekwa kuti anhydrous zvinhu zvinogona kuchinja rheological properties yekrimu.
5.3 Kugadzirisa Misimboti yeMafomura ekuzora
Anhydrous substances inonyanya kukodzera kune anhydrous systems (yakadai semafuta essences), sezvo inogona kudzivirira kuiswa kwemvura yakasununguka. Iyo monohydrate yemvura-yakavakirwa zvigadzirwa inogona kupa yakagadzikana pH nharaunda (yakayerwa fluctuation renji ± 0.2 vs ± 0.5 yeanhydrous zvinhu).
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Mhedziso uye Tarisiro
Musiyano uripo pakati pe monohydrate uye anhydrous L-cysteine ??hydrochloride hausi mutsauko wakapfava muhuwandu hwemvura, asi unosanganisira kupatsanurwa kwakarongeka kubva pakuzivikanwa kwemamorekuru kune kugadzirwa kwemaindasitiri. Nekuzivikanwa kweiyo QbD pfungwa uye kuvandudzwa kwePAT tekinoroji, akangwara crystalline mafomu anogona kubuda mune ramangwana - "adaptive crystals" inogadzirisa otomatiki mamiriro e hydration zvichienderana nehunyoro kwezvakatipoteredza. Parizvino, zvinokurudzirwa kuti pamusoro pe90% yezvakajairwa zvikumbiro sarudza monohydrate. Anhydrous zvinhu zvinofanirwa kungotariswa mune yakanyanya-inonzwa mvura, gadziriro dzakakosha kana tsvakiridzo yekutanga, uye yakanyatso kudzora mhando system inofanirwa kuumbwa.