I-L-cysteine ??hydrochloride, njengento ebalulekileyo ephuma kwi-molecule ye-bioactive, inezicelo ezibanzi kwiindawo zokutya, amayeza kunye nezithambiso. Iimveliso zayo zorhwebo ikakhulu zikhona kwiifom ezimbini - i-monohydrate equkethe amanzi ekristale kunye ne-anhydrous ngaphandle kwamanzi ekristale. Nangona ezi ntlobo zimbini zivela kwimichiza efanayo, zibonisa umahluko omkhulu ngenxa yobukho okanye ukungabikho kwamanzi ayikristale. Eli nqaku liza kuqala kwiipropati ezisisiseko zeekhemikhali kwaye zihlolisise ngokunzulu iiyantlukwano phakathi kwezi zimbini ngokubhekiselele kwizinto eziphathekayo kunye neekhemikhali, ukusetyenziswa kwezoshishino kunye noqoqosho lobugcisa, ukubonelela ngeembekiselo zesayensi kuphando kunye nophuhliso, imveliso kunye nokusetyenziswa kwiinkalo ezinxulumeneyo.

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I. Ubume beMichiza kunye neeMpawu zoLwakhiwo

1.1 Umahluko ochanekileyo wokwakheka kweemolekyuli
I-chemical formula ye-L-cysteine ??hydrochloride monohydrate yi-C?H?NO?S·HCl·H?O. Kwisakhiwo sayo se-crystal, i-molecule nganye ye-L-cysteine ????i-hydrochloride idibene ne-molecule yamanzi nge-hydrogen bond. Olu hlobo lweamolekyu yamanzi alukho ngokukhululekileyo kodwa lufakwe njengamanzi e-crystalline kwiindawo ezithile kwi-lattice, okwenza isakhiwo sokulungelelanisa esizinzile. Ngokwahlukileyo, i-chemical formula yefom ye-anhydrous yenziwe lula kwi-C?H?NO?S·HCl, kwaye iikristale zayo zicwangciswe ngokuthe ngqo ngeebhondi ze-ionic kunye ne-intermolecular forces, engenakho ukwakhiwa kwe-lattice ebandakanya iimolekyuli zamanzi.

1.2 Ubume kunye nokuThethaniswa kweZakhiwo zeCrystal
Uhlalutyo lwe-X-ray diffraction lubonisa ukuba i-crystal ye-monohydrate yeyenkqubo ye-crystal monoclinic, kunye neqela lesithuba se-P2?. Iiparamitha zeeseli zeyunithi a=7.42 A, b=6.85 A, c=10.39 A, kunye ne-β=98.5°. Ukuqaliswa kweeamolekyu zamanzi kwandisa umthamo weseli yeyunithi malunga ne-12%, ukwenza isakhiwo sesikhokelo esivulelekileyo. Nangona kunjalo, iikristale ze-anhydrous zibonisa imowudi yokupakisha edibeneyo, kwaye iipatheni zabo ze-diffraction zibonisa iimpawu eziphakamileyo kwi-2θ = 15.6 ° kunye ne-24.3 °. Le yantlukwano ichaphazela ngokuthe ngqo iipropathi ezibonakalayo zezi zimbini.

1.3 Inkxaso evela kwizibalo zethiyori
Izibalo ze-Density functional theory (DFT) zibonisa ukuba amandla okubopha ama-molecule amanzi kunye nenxalenye ye-hydrochloride kwi-monohydrate malunga -28.6 kJ / mol. Olu nxibelelwano luphakathi aluqinisekisi kuphela ukuzinza kwecrystallization kodwa luvumela iamolekyuli zamanzi ukuba zihlanjululwe ngokuphindaphindiweyo phantsi kweemeko ezithile (ezifana nokufudumeza ukuya kwi-110 ℃). Amandla e-lattice e-anhydrous crystals amalunga ne-7% ephezulu kuneekristale ze-monohydrate, ezichaza indawo yazo ephezulu yokunyibilika kodwa ukuzinza okungekuhle kokufunxa ukufuma.

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Ii. Umahluko ocwangcisiweyo kwiipropati zomzimba kunye neekhemikhali

2.1 Ulwahlulo lokuziphatha kwe-thermodynamic
Iimvavanyo ezahlukeneyo ze-calorimetry (DSC) zokuskena zibonise ukuba i-monohydrate yafumana ukunyibilika kokunyibilika kwi-175-178 ° C, ihamba kunye nencopho ye-endothermic (ΔH≈142 J / g), apho ukuchithwa kwamanzi ekristale kunye nokubola kwemolekyuli kwenzeka ngaxeshanye. Ngenxa yokunqongophala kwamanzi e-crystalline, iqondo lokushisa lokubola kwezinto ezingenamanzi liyenyuka ukuya kwi-195-200 ℃, kodwa utshintsho lwe-enthalpy lokubola luyancipha ukuya malunga ne-118 J / g. Lo mahluko ubonisa ukuba izinto ezi-anhydrous zinokuba neenzuzo kwiimeko zesicelo sobushushu obuphezulu, kodwa ifestile yabo yozinzo emxinwa kufuneka ilawulwe ngononophelo.

2.2 Uthelekiso lwekinetics yokupheliswa
Uvavanyo lokuchithwa kwamanzi kwi-25 ℃ lubonisa ukuba kuthatha imizuzwana ye-45 kuphela ukuba i-monohydrate ifikelele kwi-concentration egcweleyo (malunga ne-1.2 mol / L), kunye nobushushu be-solubility yi-15.2 kJ / mol. Nangona kunjalo, i-anhydrous substance ithatha imizuzwana ye-120 ukufikelela kwinqanaba elifanayo, kwaye ukushisa kokuchithwa ngu-19.8 kJ / mol. Lo mahluko we-kinetic uvela kwinto yokuba inethiwekhi yebhondi ye-hydrogen egcinwe ngaphambili kwi-monohydrate inokuthi idibanise iimolekyuli zamanzi ezinyibilikayo, ezibaluleke kakhulu ekulungiseleleni iinaliti zamachiza ezifuna ukuchithwa ngokukhawuleza.

2.3 Uhlalutyo lobungakanani bobumanzi Ukuziphatha kokufunxa
Uvavanyo lwe-dynamic humidity adsorption (DVS) lubonakalise umahluko ophambili: Ngaphantsi kweemeko ze-25 ℃ kunye ne-75% RH, ukuzuza ubunzima be-monohydrate phakathi kweeyure ze-48 kuphela yi-0.8%, ehambelana nemimiselo ye-pharmacopoeia. Ngaphantsi kweemeko ezifanayo, i-anhydrous substance izuza i-5.3% ubunzima kwiiyure ze-6 kwaye iguqulelwe ngokupheleleyo kwi-monohydrate emva kweeyure ze-24. Olu phawu lumisela ukuba izinto ezingenamanzi kufuneka zifakwe i-vacuum-packed kunye nefilimu edibeneyo ye-aluminium-plastiki kwaye isetyenziswe ngokukhawuleza emva kokuvulwa.

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Iii. IiNdlela eziNzulu zoZinzo kunye nokuSebenza kwakhona

3.1 Umahluko kwiindlela zokuwohloka kweekhemikhali
Uvavanyo olukhawulezayo lokuzinza (40 ℃ / 75% RH) lubonise ukuba i-oxidation-half-life yeqela le-thiol (-SH) kwi-monohydrate yayiziinyanga ze-18, kwaye imveliso ephambili yokuthotywa yayiyi-cystine. Ngaphantsi kweemeko ezifanayo, i-half-life of anhydrous substances iyancipha ukuya kwiinyanga ezili-9, kunye neemveliso ezininzi ezifana ne-hydrogen sulfide kunye ne-asidi ye-sulfurous zenziwa. Oku kubonisa ukuba amanzi e-crystalline akhusela amaqela e-thiol asebenzayo ngokwenza iibhondi ze-hydrogen, ukulibazisa inkqubo ye-oxidation.

3.2 Iimpawu ezikhethekileyo ze-slide-state reactivity
Kuvavanyo oludibeneyo lokugaya iziyobisi, i-monohydrate yayinokuhambelana kakuhle ne-magnesium stearate, kwaye akukho mpendulo yabonwa emva kweentsuku ze-60. Ngaphantsi kweemeko ezifanayo, izinto ezi-anhydrous zifumana i-acid-base reaction kunye ne-magnesium stearate, ekhokelela ekunciphiseni kweeyunithi ze-0.8 kwi-pH. Lo mahluko ubonisa ukuba kwinkqubo yokuqulunqa, ukukhethwa kwabancedisi kufuneka kuthathelwe ingqalelo imeko ye-hydration yesithako esisebenzayo seyeza.

3.3 Uphononongo oluthelekisayo ngoZinzo lokuKhanya
Uvavanyo lokubonisa ukukhanya kwe-ultraviolet (4500Lx) lubonise ukuba izinga lokugcinwa kwesisombululo se-monohydrate (5%) lali> 95% emva kweeyure ze-24, ngelixa isisombululo se-anhydrous sibonisa ukuthotywa kwe-10% kwiiyure ze-12. Kucingelwa ukuba amanzi e-crystalline anika indlela eyongezelelweyo yokukhusela ukukhanya ngokucima amandla eemolekyuli zombuso ezivuyisayo.

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Iv. Amanqaku aPhambili kwiMveliso yoShishino kunye noLawulo loMgangatho

4.1 IiParameters eziphambili zenkqubo ye-crystallization
Imveliso yemveliso ye-monohydrate ithatha indlela yokupholisa i-crystallization: ngokulawula izinga lokupholisa le-0.5 ℃ / min, ukushisa kwe-terminal ye-4 ℃, kunye nesantya esishukumisayo se-120rpm, iikristale eziqhelekileyo ezinobungakanani be-particle D50 = 180μm zingafumaneka. Izinto ze-anhydrous zifuna i-crystallization ye-solvent eguqukayo usebenzisa i-solvents engekho emanzini (njenge-ethanol ye-anhydrous), eyandisa inkqubo yobunzima nge-30% kwaye idinga ukukhuselwa kwe-nitrogen ukukhusela ukufunxa ukufuma.

4.2 Umahluko kwimigangatho yolawulo lomgangatho
I-European Pharmacopoeia ichaza ukuba umswakama we-monohydrate kufuneka ube ngu-7.5-9.5%, kwaye intsalela ekutshiseni kufuneka ibe ngu-≤0.1%. Izinto ze-anhydrous zifuna umxholo womswakama we-≤0.5%, kodwa umda wesinyithi esinzima unzima (≤5ppm vs ≤10ppm ye-monohydrate). Lo mahluko usemgangathweni ubonakalisa iindlela ezahlukeneyo zamanqaku anokubakho emngciphekweni.

4.3 IiMfuno eziKhethekileyo zokugcina nokuthutha
I-Monohydrate ingagcinwa ngokuqhelekileyo kwindawo epholileyo (

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V. UbuChule bokuKhetha ubuNzululwazi kwiimeko zeSicelo

5.1 Ingqiqo ekhethwayo yoshishino lokutya
Kwizicelo zokubhaka, i-monohydrate iye yaba yeyona nto iphambili ngenxa yokuchithwa kwayo ngokukhawuleza kunye nomlinganiselo ofanelekileyo. Idatha evela kwishishini elithile lezizwe ngezizwe libonisa ukuba ukusetyenziswa kwe-monohydrate kunokunciphisa ukusetyenziswa kwamandla kwintlama evuselela nge-15% kunye nokwandisa umthamo othile wemveliso egqityiweyo nge-8%. Kuphela kwintlama yeswekile ephezulu kakhulu (umxholo weswekile> 30%), uphawu olusezantsi lokufuma kwezinto ezingenamanzi lunokuba luncedo ekubambezeleni ukusabela kwe-Maillard.

5.2 Umthi weSigqibo kuMmandla woShishino
Izitofu kufuneka zisebenzise i-monohydrate (ichazwe ngokucacileyo kwi-USP43-NF38); Kwiifom zedosi eqinile yomlomo, ukuba i-API inovelwano kumswakama (ofana ne-amoxicillin kunye ne-clavulanate potassium), ukufaneleka kwezinto ezingenamanzi kufuneka zihlolwe; Amalungiselelo eengqungquthela anokukhethwa ngokuguquguqukayo, kodwa kufuneka kuqatshelwe ukuba izinto ezingenamanzi zingatshintsha iimpawu ze-rheological ze-cream.

5.3 Imigaqo yoHlengahlengiso kwiiFomula zokuCosmetic
Izinto ze-anhydrous zifanelekile ngakumbi kwiinkqubo ze-anhydrous (ezifana ne-oily essences), njengoko zinokuthintela ukuqaliswa kwamanzi akhululekile. I-monohydrate yeemveliso ezisekelwe emanzini zinokubonelela ngemeko-bume ye-pH ezinzile (uluhlu lokuguquguquka olulinganisiweyo ± 0.2 vs ± 0.5 yezinto ezingenamanzi).

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Isiphelo kunye neProspect

Ukwahlula phakathi kwe-monohydrate kunye ne-anhydrous L-cysteine ??hydrochloride ayikho nakancinane umehluko olula kumxholo wamanzi, kodwa kubandakanya ulwahlulo olucwangcisiweyo ukusuka ekuqaphelisweni kwe-molecular ukuya kwimveliso yezoshishino. Ngokuthandwa kwengcamango ye-QbD kunye nophuhliso lwetekhnoloji ye-PAT, iifom ze-crystalline ezikrelekrele zinokuvela kwixesha elizayo - "iikristale eziguquguqukayo" ezilungelelanisa ngokuzenzekelayo i-hydration state ngokuhambelana nokufuma kwendalo. Okwangoku, kucetyiswa ukuba ngaphezu kwe-90% yezicelo eziqhelekileyo zikhetha i-monohydrate. Izinto ze-anhydrous kufuneka ziqwalaselwe kuphela kumanzi amaninzi, amalungiselelo akhethekileyo okanye uphando olusisiseko, kwaye inkqubo yokulawula umgangatho ongqongqo kufuneka isekwe.