Yakanyanya kukwirira \ / yakadzika tembiricha uye yakajeka yekufumisa madhara pane sampuli kugadzikana: fungidziro & madzinza

Stability fundo ongorora kuti kuongorora samples (i.e., mishonga madiki madiki mamalecules, kushomeka kwemasita pasi pekunze Yakakwira- uye yakaderera-yekuchengetedza inogona kuunza makemikari kusvibiswa, shanduko yemhando, kana chikamu chekuparadzaniswa; Kufumurwa kwakasimba kwechiedza kunogona kukonzera kusungwa kwekuchena kana yemahara-maneji manhau yekuita, ichikonzera PhotoDogradation. Kuongorora zvakarongeka kuongorora kwe physicochemical mhedzisiro ye40 ° C, -20 ° C, uye chiedza pamhando dzakasiyana siyana dzeenzaniso dzakakosha kuti uve nechokwadi chekuvimbika uye kuvimbika. Iri pepa rinotarisa pane dzidziso yekufunga uye maitiro ekusarudza aya matatu mamiriro ezvinhu akanyanyisa pamamolekyudhi madiki, mishonga yerimbi-ion, uye inopa mishonga inoenderana uye yekuongorora inoenderana uye yekuongorora.

1. Kupisa kwakanyanya sei (40 ° C) kunokanganisa madiki madiki & mression ion?

Tembiricha yakakwira inowedzera maitiro ekugadzirisa, kazhinji inowedzera organic molecule decrucule yekugadzirisa uye inoparadza inoshanda zvinongedzo. Mune mishonga yekukudzika yakagadzikana, 40 ° C \ / 75% rh inoshandiswa semamiriro ekukurumidza kufanotaura maitiro ekupedzisira. Kukwidziridzwa kwakasimudzirwa kunogona kuunza oxidation, hydrolysis, kushomeka, kana isomerization mumamolekyudhi madiki, uye inogona kushandura zvakare simbi-ion yekubatana uye solubility.

1.1 ZVINOKOSHA ZVINOGONESESA PAKUTI MOLECULES

• Oxidative kusvibiswa:LIPIDS kana zvimisikidzo zviri nyore oxidize pa40 ° C, kugadzira zvigadzirwa zvekushambadzira.
  
  

• Hydrolysis:Ester kana maAppride zvisungo zvinonyatsoita nyore kana kutyisa, kutevedzera acids, zvigadziko, kana zviga.
  
  

• Isomerization:Cis-Trans Shanduko kana Railmization inogona kuderedza chiitiko.
  
  

Muenzaniso: rapamycin (uye yayo iv prodrug cci-779) yakachengetwa pa40 ° C \ / 75% Oxidative \ / Hydrolytic kusvibiswa-kwakakwirira kupfuura samples pa25 ° C. Nekudaro, zvinoshanda zvemukati uye zvinoshandura zvinosvibisa zvinofanirwa kutariswa zvakanyanya pasi pekupisa kushushikana.

1.2 Kiyi mhedzisiro pamasimbi-ion mhinduro

• Kugadzikana kugadzikana:Metal-ligand kuenzana Constants inosiyana nekushisa; Carsexical dzisina kusimba dzinogona kuburitsa, kusunungura mahara.
  
  

• Solubility & Sporipitation:Nepo vazhinji vesimbi vanonyungudika zvakanyanya kuT, vamwe (i.e., hydroxides, mamwe madhiri) anogona kuita shanduko kana kufungidzira. Calcium kabhoni, semuenzaniso, inoumba hydrate dzakasiyana pane dzakasiyana tembiricha, inokanganisa likecipoter morphology.
  
  

• Oxidation nyika inoshanduka:Fe²⁺ anogona oxidize kune fe³⁺ kuEast t
  
  

Pa40 ° C, tarisa kuoma kunzwisisa uye kusarudzika njodzi yekudzivirira kusarasikirwa kweIsion kana kutaura kwekuchinja.

1.3 Kugadzira yakakwira-tembiricha kugadzikana bvunzo & kuyerwa nzira

Maitiro akajairika ekuongorora anosanganisira:

• DSC (Yakasiyana Scanning Calorimetry):Matanho anogadzikana anodzika, thaasiti yekushandurwa, uye mishonga inopinda.
  
  

• UV-VIVER Spectrophotometry:Maturakiti ekutora kana ruvara shanduko kuti udzikiswe inoshanda yekushandisa kana kusvibiswa kwekugadzira nguva.
  
  

• ICP-MS \ / AAS:Chaizvoizvo inojekeswa nesimbi-ion kutarisisa, kuona kurasikirwa kana kufungidzira pre- uye kutumira-kupisa-kurapwa.
  
  

• Hplc \ / GC-MS:Inoparadzanisa uye inoratidza zvigadzirwa zvekushambadzira, kuverenga kudzoreredza kwevabereki kuwanda.
  
  

Semuenzaniso protocol: Isa samples mu40 ° C Mvura yekugezesa yekuwedzera kuchembera; Nguva nenguva mhanya DSC Scans zviitiko zvezviitiko zveTermal, kuyera UV-VIVEL ASTORBANCE, uye shandisa ICP-MS kutevedzera masimbi-ion. Pamwe chete nzira idzi dzinopa maonero akakwana ekuchinja-kupisa-kusakara.

2.

At -20 ° C, kutonhora inoshandura nzira dzenyama, zvingangoita kukonzera kupatsanurana kana kugadzikana kuchinja. Ice makristuru kunze kwekunyora kupinda mumabhodhi asina kujairika, kupomera nzvimbo yemuno uye pH, iyo inogona kukonzera zvisingatarisirwi maitiro kana maPripitates. Yakadzokororwa emahara-thaw matanda anogona kukanganisa maitiro ekuenzanisira uye kutendeka.

2.1 Freeze-thaw mhedzisiro pamamorekuru madiki

Munguva yeGreale-thaw, solutes inotarisa kutenderedza makristasi echando, kazhinji anodzokororwa kana kuunganidza pa thawing. Macroscopicy izvi zvinowoneka seuruso kana kufungidzira; microscopically, molecular yekugadzirisa kana kukuvara kunoitika. Zvidzidzo muDMSO-based Compound Limbary inoratidza akawanda freeze-thaw clezhanyama inoderedza inoshanda Systems inowedzera kupatsanurwa chikamu inoda kudzora kutenderera kwekutenderera uye kugadzikana kwekutarisa.

2.2 michina muhomwe mune yesimbi-ion mhinduro

Ice Foration inosundira simbi ion uye inowedzera muzvinyorwa zvemvura, kwenguva pfupi kukwidzirisa h⁺ kusimbisa. Ye zero-valent iron (ZVI), freeze-free-thaw inotarisa mapurotoni anodzungudza denderedzwa reSefsivation; Akaburitswa metals (i.e., ni²⁺) desorb, uye maitiro afare anogona kuzvinamatira. Akadaro Ph uye ion swings inogona kushandura mamiriro eposme uye kuongorora, kunokanganisa kugadzikana kwakazara.

2.3 Kuyera Yemahara-Thaw Improcts

• DLS (Dynamic Light kupararira):Tracks trackle-saizi inoshandura pre- uye post-thaw kuti uone kushamisika.
  
  

• ICP-MS \ / AAS:Matanho esimbi-ion kusarudzika misiyano isati yatanga uye mushure mekusununguka-thaw kuti uongorore kurasikirwa kana kufungidzira.
  
  

• Quantitative freeze-thaw cycling:Tevera ICH Nhungamiro (i.e., Matatu Cendery: -10 kusvika -20 ° C ye 2days, ipapo 40 ° C for 2days) Nekutenderera mushure mekutenderera kwega kwega kwekuongorora.
  
  

Kuburikidza nemaitiro aya, maLabs anokwanisa kudzora-thaw mhedzisiro uye optimize chengetedzo \ / kufambisa protocol.

3. Maitiro ekuyera mafoto emitero yemifananidzo yemijemsensitive?

Compound neConjugated π-Systems, Anonhuhwirira Mhete, kana Simbi Inonyora Uv \ / mifananidzo inooneka uye pasi pepikicha, PhotoOxidation, kana yemahara-emahara makenduru. Kunzwisisa izvi michina kunokosha kuti ugadzirise mwenje-kugadzikana bvunzo uye kufanotaura Photoproducts.

3.1 Ndeapi ma compounds ane chiedza-chinonaka & nei?

• Dhayi ine masisitimu akakomberedzwa kana simbi-kusanzwisisana-contorines nyore nyore kutora mwenje uye kujekesa zvindori kana zvisungo, kugadzira radicals.
  
  

• Mafuta anoshamisa mumakwenzi emakwenzi anogona kuputika kana kuora pasi peUV \ / kupisa.
  
  

• Mamolekyuli ane kushaikwa kushaya simba (i.e., nitroso, peroxide) anonyanya kufarirwa kufananidzira PhotoDogradation.
  Chero chipi zvacho chivakwa chine chromophores kana foto-clapable zvisungo zvinogona kuitwa photochemistry-ionzation, kuwedzera, isomerization-uye goho rakachinjirwa kana rakashongedzwa.
  
  
  

3.2 yakatarwa Photostability yekuyedza dhizaini

Per ich q1b:

• Yakamanikidzwa-Dhairasi Stage: kufumura samples kune hutsinye mwenje kumepu ese angangove anokwanisa degradants.
  
  

• Specionation Stage: Nyorera iyo yakatsanangurwa mwenje dhizi kuti uongorore kusimba kusimba.
  ZVINOKOSHA ZVINOKOSHA:
  
  

• Chiedza Tsime: Simbisa Chiedza (D65 \ / ID65 Fluorescent Lamps, Xenon-Arc, Metal-Offer Lamps <320nm \ / / / / / / / Uva uye inooneka mwenje.
  
  

• Sampula Setup: Nzvimbo mune Intert, inowoneka midziyo, yakaiswa pasi peunifomu yekuratidzwa kwunifomu, ine rima control. Kana kukurumidza kurira kusvibiswa kunoitika, kupfupisa nguva yekufumura nguva \ / kuwedzera.
  
  

• DEGE KUTAMBIRA: Calibrate Iradance
  
  

STRITSIRT Control uye Rima \ / Kuenzanisa Kuenzanisa Kubereka Kuvimbika PhotoStability data uye mechanistic nzwisiso.

3.3 PhotoDogradation Kinetic Modeling

Photodegradation kazhinji inotevera yekutanga-kurongeka kinetics:

C (t) = c0e-ktc (t) = c_0 e ^ {- kt}

Iko k chiyero chinogara chichigara. Kumusoro-mharidzo maitiro kunogona kukodzera iyo Langmuir-Hinshelwood Model. Nekutevera kuteedzera kuburikidza neUV-vis kana HPLC-ms nekufamba kwenguva, k inogona kuve yakakodzera. Iyo photochemical Quantum govert (φ) -Memolecules yakaita nePhoton yakanyudzwa-inoverengerwa nekuenzanisa chiyero chekusvibisa neCocient Photon Flux. Iyi parameter inokoshesa mwenje-kugadzikana.

4. Yakakurudzirwa Kugadzikana-kuyerwa nzira

Sanganisa akawanda ekuongorora maitiro eiyo yakazara kugadzikana chimiro:

• Yakakwira-T \ / Freeze-thaw:
  - DSC yezviitiko zvekupisa \ / Chikamu Shanduko
  - UV-VIS yekutarisa inoshanda kana ion constantration
  - ICP-MS \ / ANAS yeSimbi kuwanda
  - DLS yeChikamu \ / Aggregation Ongororo
  
  

• Photosting:
  - UV-VIS KINITSAIC ADENGE KUTAMBURA
  - HPLC-MS yeiyo inoshatiswa chiratidzo uye inosara kuwanda
  - Quantum gogo uye kuyera nguva dzose kuverenga kwakavakirwa pane calibrated mwenje
  
  

Ita shuwa zvakadzama kudzora (kusviba, zvakasiyana-siyana zviyero), zvinoperekedza, uye kurapwa kwehuwandu kuti zvisimbise mibairo.

5. Kubudirira Kuzivisa kweData Rokugadzikana

Kuti uburitse zvakawanikwa zvakajeka, gadzirira:

• Conceentration vs. Nguva plots: Enzanisa anoshanda kana ion mazinga ari pasi pe40 ° C vs. -20 ° C.
  
  

• Photodegradation Kinetics Curves: Ratidza kusungwa kana kutora vs. kujekesa nguva \ / dosi, kusanganisira logarithmic inokodzera.
  
  

• DSC Thermograms: Ratidza Engedo \ / Exotherms yeChikamu Shanduko kana kuora kwechiitiko pakupisa.
  
  

• Process Diagrams: Enzanisira Offze-Thaw kutenderera kukanganisa kana kuchengetedza \ / kutakura mabasa.
  
  

Akanyatsogadzirwa zviono zvekutsigira kududzira uye kukurukurirana.

Mhedziso

Kushushikana kwakasiyana kukanganisa nzira dzakasiyana-siyana. Kuchengetera uye kutakurwa kunofanirwa kuve kwakagadziriswa: zvakareruka-zvinonyanyisa zvinhu mumidziyo yeOpaque, zvinyoronyoro-zvinyoronyoro mune tembiricha makiromita ekutonhora, uye svutugadzike masisitimu anotonhora kana mvura-nitrogen setups. Basa remangwana rinofanira kuongorora kusanganisa kushungurudzika (i.e., kupisa + mwenje) kunatsa kutarisirwa kwakarongeka.

Zvimwe zvinyorwa

• Units:Chiedza dosi mune j \ / m² kana lux-maawa; rate nguva dzose k muzuva; Quantum Govera φ; zvakasara zvemukati se%.
  
  

• Zvikamu zveMuenzaniso:Gadzirisa protocol pane chikamu (API, yepakati, mostation
  
  

Referensi: Kubva paICH Q1A \ / Q1B mirayiridzo, uyo kugadzikana Annex 10, uye zvinyorwa zvazvino.