Shaanxi BLOOM Tech Co., Ltd. yog ib tug ntawm cov uas paub txog manufacturers thiab lwm tus neeg ntawm mirtazapine ntsiav tshuaj 30mg nyob rau hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo mirtazapine ntsiav tshuaj 30mg rau muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Mirtazapine ntsiav tshuaj 30 mgyog ib qho tshuaj tiv thaiv kev ntxhov siab hauv qhov ncauj uas yog cov tshuaj tetracyclic antidepressants (TeCA) thiab raug cais raws li ob qho tib si noradrenergic thiab tshwj xeeb serotonergic antidepressants (NaSSA). Nws cov ntsiab lus tseem ceeb, mirtazapine, siv cov tshuaj kho mob los ntawm ntau yam neurotransmitter tswj cov txheej txheem. Lub alpha ₂ receptor antagonizes thiab thaiv lub hauv paus presynaptic membrane alpha ₂ receptors, tshem tawm cov lus pom tsis zoo inhibition ntawm kev tso tawm ntawm norepinephrine (NE) thiab serotonin (5-HT), yog li txhim kho adrenergic thiab serum neurotransmission. Cov txheej txheem no ncaj qha nce qhov concentration ntawm NE thiab 5-HT hauv lub hlwb, txhim kho cov tsos mob ntawm kev xav tsis zoo thiab tsis muaj kev txhawb siab. Nws tuaj yeem ua ke nrog cov neeg mob pw tsaug zog lossis tsis qab los noj mov (vim H ₁ receptor antagonism). Xav tau cov tib neeg uas muaj kev cuam tshuam me me rau kev ua haujlwm ntawm kev sib deev (piv rau SSRIs, qhov tshwm sim ntawm kev sib deev tsis zoo yog txo los ntawm 40%). Nws raug nquahu kom noj cov tshuaj ntxiv rau 4-6 lub hlis kom txog thaum cov tsos mob ploj tag. Sudden discontinuation ntawm cov tshuaj yuav ua rau cov tsos mob rov qab.
Peb cov khoom
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Mirtazapine COA
Lub Polycrystalline Phenomenon ntawm Mirtazapine: Khawv koob thiab Kev Sib Tw ntawm Homogeneous Anomalies
Hauv kev txhim kho tshuaj, qhov tshwm sim ntawm ntau cov qauv siv lead ua tsim los ntawm tib lub molecule nyob rau hauv txawv crystallization tej yam kev mob, hu ua polymorphs, yeej ib txwm yog ib tug tseem ceeb variable cuam tshuam rau kev ua tau zoo ntawm cov tshuaj. Noj cov tshuaj antidepressantMirtazapine ntsiav tshuaj 30 mgRaws li ib qho piv txwv, nws cov mis molecular yog C17H19N3, tab sis los ntawm kev hloov cov kuab tshuaj, qhov kub thiab txias, los yog crystallization txheej txheem, cov ntaub ntawv sib txawv crystal tuaj yeem tsim. Qhov sib txawv ntawm solubility, dissolution npaum li cas, stability, thiab bioavailability ntawm cov ntaub ntawv siv lead ua no yuav ncaj qha txiav txim qhov kev kho mob thiab kev nyab xeeb ntawm cov tshuaj:
Molecular Code of Mirtazapine: A "Neural Regulatory Network" nrog plaub lub nplhaib qauv
Mirtazapine belongs rau tetracyclic piperazine pyridine derivative, thiab nws cov qauv molecular ua tiav cov txiaj ntsig zoo ntawm cov tshuaj tiv thaiv kev ntxhov siab thiab kev pab pw tsaug zog los ntawm ob lub tswv yim ntawm kev ua:
Norepinephrine system txhim kho
Raws li ib tug presynaptic ₂ receptor antagonist, mirtazapine thaiv qhov tsis zoo tawm tswv yim inhibition ntawm NE tso tawm los ntawm nws tus kheej receptors, txhim khu kev ua haujlwm ntawm locus coeruleus (LC) neurons, ua kom lub latency rau pw tsaug zog, thiab txo qis thaum hmo ntuj awakenings. Qhov kev sim pom tau hais tias ntawm ib koob ntawm 5mg / kg, kev ua haujlwm tawm ntawm NA neurons hauv locus coeruleus ntawm nas tau nce ntau.
Serotonin tuaj yeem tswj lub cev
Los ntawm antagonizing 5-HT ₂ C receptors, mirtazapine relieves nws inhibition ntawm DA thiab NE tso; Ib txhij thaiv 5-HT receptor thiab txo cov tshuaj tua kab mob vim xeev siab thiab ntuav. Hauv kev tshawb fawb vivo tau lees paub tias nws tuaj yeem txhaj tshuaj raws li kev txhim kho kev tua hluav taws ntawm 5-HT neurons.
Histamine system sedation
Nws cov nyhuv antagonistic muaj zog ntawm H ₁ receptors muab nws benzodiazepine zoo li cov nyhuv sedative, tab sis tsis muaj cov khoom siv ntxiv. Cov ntaub ntawv kho mob qhia tau hais tias ib koob tshuaj 15mg / hnub tuaj yeem txo lub sijhawm rau cov neeg mob pw tsaug zog 22 feeb thiab ncua sijhawm tag nrho pw tsaug zog 1.1 teev.
Qhov ntau- lub hom phiaj ntawm kev ua haujlwm no ua rau mirtazapine yog ib qho ntawm cov tshuaj nyiam los kho kev nyuaj siab ua ke nrog insomnia, tab sis nws cov qauv molecular hloov tau kuj muab lub hauv paus rau kev tsim ntawm polymorphs.
Molecular ballet ntawm polymorphic phenomena: dynamic tshuav ntawm conformation thiab stacking
Polymorphic phenomenon ntawmMirtazapine ntsiav tshuaj 30 mgyog vim qhov yooj ntawm nws cov molecular conformation thiab ntau haiv neeg ntawm intermolecular rog. Raws li kev faib tawm crystallographic, nws cov polymorphs tuaj yeem muab faib ua conformational polymorphs thiab conformational polymorphs:
Conformational polymorph: Kev hloov pauv hloov ntawm cov pob txha molecular ua rau muaj kev hloov pauv hauv hom stacking. Piv txwv li, nyob rau hauv cov kuab tshuaj diffusion crystallization, lub π - π kev sib cuam tshuam deb ntawm cov benzene rings ntawm mirtazapine molecules yog luv los ntawm 3.6 Å mus rau 3.35 Å, tsim ib tug tighter lattice qauv thiab ua rau ib tug txo nyob rau hauv solubility.
Polycrystalline configuration: Kev kho kom zoo ntawm molecular chiral chaw ua rau muaj qhov sib txawv. Sab laug- tes enantiomer (S-enantiomer) ntawm mirtazapine nyiam blocks alpha ₂ thiab 5-HT ₂ receptors, thaum sab xis- tes enantiomer (R-enantiomer) tshwj xeeb thaiv 5-HT receptors ∝ Qhov kev sib txawv ntawm cov qauv no tuaj yeem cuam tshuam los ntawm qhov sib txawv ntawm qhov sib txawv ntawm cov qauv molecular hauv cov lattice.
Tsim mechanism:
Cov nyhuv hnyav: Hauv DMSO, mirtazapine tsim ib daim ntawv siv lead ua metastable vim muaj kev koom tes ntawm cov kuab tshuaj molecules hauv hydrogen bonding tes hauj lwm, thiab nws qhov kev sib cais yog 40% siab dua li cov khoom ethanol crystallization.
Kub gradient: Hauv programmed cooling crystallization, kev kho cua sov saum toj no 75℃tuaj yeem hloov pauv siv lead ua daim ntawv II mus rau hauv cov siv lead ua ruaj khov dua I, nrog cov ntsiab lus melting ntawm 168℃mus rau 172 degree.
Mechanical action: Pob milling kev kho mob ua rau lub lattice tsis xws luag, nce cov ntsiab lus amorphous los ntawm 5% mus rau 18%, cuam tshuam rau kev ua haujlwm compression.
Daim ntawv qhia "kev ua tau zoo" ntawm cov ntaub ntawv polymorphic: dhia los ntawm chav kuaj mus rau kev kho mob
Qhov sib txawv ntawm physicochemical zog ntawm cov ntaub ntawv sib txawv siv lead ua ncaj qha txiav txim siab txoj kev loj hlob ntawm mirtazapine formulations:
Solubility thiab dissolution tus nqi: tus yuam sij rau bioavailability:
Crystal form A (metastable state): Lub solubility nce mus txog 0.8mg/mL hauv pH 6.8 buffer tov, thiab tus nqi dissolution tas li (k) yog 0.12min ⁻¹. AUC ₀₋₂₄ h hauv beagle dev yog 2.6 npaug siab dua li ntawm crystal form B.
Crystal form B (lub xeev ruaj khov): Lub solubility tsuas yog 0.4mg / mL, tab sis cov tshuaj lom neeg ruaj khov zoo heev. Tom qab khaws cia ntawm 40℃/ 75% RH rau 6 lub hlis, qhov nce ntawm cov khoom muaj feem xyuam yog tsawg dua 0.3%.
Qhov tseem ceeb hauv kev kho mob: Rau BCS chav kawm II (tsawg solubility siab permeability) tshuaj mirtazapine, xaiv ib daim ntawv siv lead ua metastable tuaj yeem txhim kho qhov ncauj bioavailability, tab sis qhov kev pheej hmoo ntawm crystal transformation yuav tsum tau tswj los ntawm micronization technology (d ₉₀<25 μ m) and coating process.
Moisture absorption thiab stability:
Qhov "invisible threshold" ntawm formulation technology:Ib nrab hydrate siv lead ua daim ntawv: Hauv 75% RH ib puag ncig, nws nqus dej noo thiab nce qhov hnyav los ntawm 8% hauv 24 teev, hloov mus rau hauv dihydrate thiab ua rau cov formulation mus clump.
Anhydrous crystal form: hygroscopic hnyav nce<1%, but it is necessary to control the residual crystallization solvent (DMSO<500ppm), otherwise it may induce crystal transformation.
Kev tswj cov txheej txheem: Kev ziab kom qhuav yog siv los npaj amorphous mirtazapine, uas tuaj yeem zam qhov tsim ntawm hydrates, tab sis qhov kub thiab txias ua ntej (-45 degree) thiab sublimation tus nqi (0.5℃/ min) yuav tsum tau kho kom zoo los tiv thaiv iav hloov.
Powder zog: "lub cev lub hauv paus" ntawm formulation ntau lawm:
Crystal form C (koob zoo li tus): nrog lub kaum sab xis ntawm 45℃thiab cov dej tsis zoo, nws yuav tsum tau txhim kho los ntawm kev ntxiv 2% silica.
Crystal form D (block): angle of repose 28 °, can be directly used for dry granulation, but has poor compressibility (elastic recovery rate>15%).
Kev daws: npaj spherical hais (d ₀=50 μ m) los ntawm cov tshuaj tsuag kom qhuav, kom cov fluidity (Karl index<18%) and compressibility (compressibility<25%) meet the standard at the same time.
Polycrystalline 'Research Toolbox': Los ntawm Kev Ntsuam Xyuas Cov Qauv rau Kev Tswj Xyuas Txheej Txheem
Ib leeg siv lead ua X-ray diffraction (SXRD) qhia txog qhov muaj nyob ntawm N-H ··· O=C hydrogen bonding network ntawm molecules hauv crystal form A, nrog lub zog lattice 12 kJ / mol qis dua li ntawm crystal form B, piav qhia nws cov solubility ntau dua.
Powder X-ray diffraction (PXRD): Tsim kom muaj ib lub tsev qiv ntawv zoo tshaj plaws rau siv lead ua daim ntawv A (2 θ=12.4℃, 19.7℃, 24.1℃) nrog rau kev kuaj pom tsis pub dhau 0.1%, siv rau kev tswj cov khoom siv raw.
Differential Scanning Calorimetry (DSC): Crystal form A qhia txog qhov kawg ntawm qhov kawg (melting) ntawm 162 degree, thaum siv lead ua daim ntawv B nthuav tawm lub ncov exothermic (crystallization) ntawm 170 degree, tso cai rau kev soj ntsuam ntau ntawm cov sib xyaw siv lead ua piv.
Thermogravimetric tsom xam (TGA): Tshawb xyuas 0.8% ntawm cov dej siv lead ua hauv siv lead ua C, teem caij kom qhuav kom qhuav.<80 ℃ to avoid dehydration and crystal transformation.
Raman spectroscopy: Crystal A nthuav tawm lub ncov muaj zog ntawm C=O stretching vibration ntawm 1640cm ⁻¹, thaum siv lead ua B qhia kev hloov pauv liab ntawm lub ncov no mus rau 1625cm ⁻¹, uas yog siv tiag tiag - lub sijhawm saib xyuas cov txheej txheem tsom xam tshuab (PAT).
Solid state nuclear magnetic resonance (ssNMR): Distinguishing local motion sib txawv ntawm molecular chains nyob rau hauv cov ntaub ntawv siv lead ua thiab piav qhia qhov sib txawv ntawm kev sib cais.
Qhov 'kev sib tw tsim kho' ntawm polymorphs: ntsuas cov txheej txheem los ntawm kev kuaj mus rau kev ua lag luam
Patent barriers thiab generic tshuaj txhim kho
Cov tshuaj qubMirtazapine ntsiav tshuaj 30 mgtau txuas ntxiv lawv lub sijhawm ua lag luam monopoly los ntawm patented siv lead ua daim ntawv B. Generic tshuaj tuam txhab uas muag yuav tsum tau tsim non-fringing siv lead ua cov ntaub ntawv:
Crystal form E (eutectic): tsim ib qho 1: 1 eutectic nrog succinic acid, nce solubility los ntawm peb zaug, tab sis nws yuav tsum tau ua pov thawj los ua bioequivalence nrog thawj daim ntawv siv lead ua.
Daim ntawv tsis tau txhais: npaj los ntawm HME (kub yaj extrusion) thev naus laus zis, dhau ntawm cov ntawv siv lead ua patent, tab sis yuav tsum muaj teeb meem kev ruaj ntseg (crystallinity<5% after 6 months).
Polycrystalline transformation tuaj yeem ua rau muaj kev hloov pauv hauv kev kho mob:
Case: A generic drug company was forced to recall its products due to an increase in nighttime awakenings of patients caused by failure to control the content of crystal form A (>15%).
Kev daws: Tsim kom muaj txoj kev tshawb pom sai raws li PXRD los tswj cov impurity ntawm crystal form A hauv<3%.
Cov txheej txheem ntau lawm optimization
Nruam crystallization txheej txheem tuaj yeem txhim kho qhov rov ua dua ntawm cov qauv siv lead ua:
Cov ntaub ntawv sib piv: Cov ntsiab lus ntawm siv lead ua daim ntawv B hloov pauv los ntawm ± 8% ntawm cov khoom siv sib cuam tshuam crystallization, thaum qhov kev hloov pauv ntawm cov txheej txheem crystallization tas li poob mus rau ± 2%.
Kev xaiv cov khoom siv: Kev siv cov khoom sib xyaw ua ke sib xyaw ua ke (MSMPR) crystallizer, cov khoom siv lead ua tau zoo tswj tau los ntawm kev kho lub sijhawm nyob (15-30 feeb).
Mirtazapine ntsiav tshuaj yog qhov kev xaiv zoo tshaj plaws rau kev tswj kev ntxhov siab thiab kev ntxhov siab, muab cov txheej txheem tshwj xeeb ntawm kev ua haujlwm thiab muaj txiaj ntsig zoo rau cov kev mob tshwm sim hauv qee cov neeg mob. Los ntawm kev nkag siab txog nws cov tshuaj pharmacokinetics, kev siv tshuaj kho mob, kev ua tau zoo, thiab kev nyab xeeb profile, cov kws kho mob tuaj yeem txhim kho kev siv mirtazapine los txhim kho cov txiaj ntsig ntawm tus neeg mob. Txawm li cas los xij, ua tib zoo saib xyuas thiab ua raws li cov lus qhia noj tshuaj yog qhov tseem ceeb kom txo qis kev pheej hmoo ntawm kev mob tshwm sim thiab kev cuam tshuam ntawm cov tshuaj. Ib yam li txhua yam tshuaj, cov neeg mob yuav tsum tau txhawb kom sib tham qhib nrog lawv cov kws kho mob txog lawv cov tsos mob, kev txhawj xeeb, thiab kev nyiam kho mob kom ntseeg tau tias muaj kev saib xyuas zoo tshaj plaws.
Cov lus nug nquag
Puas yog mirtazapine tib yam li Xanax?
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Puas yog mirtazapine tib yam li Xanax?Xanax thiab mirtazapine yog ob hom tshuaj sib txawv. Mirtazapine yog tetracyclic antidepressant siv los kho cov kev nyuaj siab loj, thaum Xanax yog benzodiazepine siv feem ntau los kho kev ntxhov siab thiab ntxhov siab.
Leej twg xav tau mirtazapine?
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Vim li cas cov tshuaj no thiaj li muab tshuaj? Mirtazapine yog sivkho kev nyuaj siab. Mirtazapine yog nyob rau hauv ib chav kawm ntawm cov tshuaj hu ua antidepressants. Nws ua haujlwm los ntawm kev nce qee yam kev ua ub no hauv lub hlwb kom tswj kev puas siab puas ntsws.
Dab tsi yog lwm txoj hauv kev rau mirtazapine rau kev pw tsaug zog?
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"Kev hloov pauv ntau rau Mirtazapine rau kev kho mob ntawm kev ntxhov siab thiab kev nyuaj siab suav nrog Escitalopram thiab Fluoxetine.Trazodone yog lwm txoj hauv kev siv rau kev pw tsaug zog. Trazodone tshwj xeeb yog siv rau cov neeg mob uas xav tau kev pw tsaug zog zoo dua yam tsis muaj Mirtazapine qhov tshwm sim ntawm qhov hnyav nce. "
Dab tsi yog cov txiaj ntsig ntawm kev noj tshuaj mirtazapine?
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Mirtazapine yog ib qho tshuaj antidepressant. Nws yog siv loskho kev nyuaj siab thiab qee zaum obsessive compulsive disorder (OCD) thiab kev ntxhov siab. Nws ua haujlwm los ntawm kev nce siab ntau ntxiv - txhim kho cov tshuaj hu ua noradrenaline thiab serotonin hauv koj lub hlwb.
Vim li cas mirtazapine thiaj li nyuaj los tawm?
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Vim tias mirtazapine hloov pauv cov tshuaj hauv lub hlwb uas tswj cov kev xav, thaum tus neeg tsis noj cov tshuaj mirtazapine, lub cev yuav xav tau sijhawm los kho. Vim li no, maj mam tapering tawm cov tshuaj yuav pab txo tau ntau yam tsos mob.
Cim npe nrov: mirtazapine ntsiav tshuaj 30mg, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom