Hydroxypropyl methylcellulose (HPMC)
Gulu: zipangizo zokutira; Zipangizo za Membrane; Zipangizo za polima zoyendetsedwa ndi liwiro kuti zitulutse pang'onopang'ono; Chothandizira kukhazikika; Chothandizira kuimika, guluu wa piritsi; Chothandizira kumatirira cholimbikitsidwa.
1. Chiyambi cha malonda
CHOPANGIDWACHI NDI CHOSAKHALA NDI MA CELLULOSE ETHER, chomwe chimawoneka ngati ufa woyera, chopanda fungo komanso chopanda kukoma, chosungunuka m'madzi ndi zinthu zambiri zachilengedwe, chotupa m'madzi ozizira kuti chikhale choyera kapena chosungunuka pang'ono. Yankho lamadzi lili ndi ntchito pamwamba, lowonekera bwino komanso lokhazikika. HPMC ili ndi mphamvu ngati gel yotentha. Pambuyo potenthetsa, yankho lamadzi la chinthucho limapanga mpweya wa gel, kenako limasungunuka pambuyo pozizira. Kutentha kwa gel kwa mitundu yosiyanasiyana kumakhala kosiyana. Kusungunuka kumasintha ndi kukhuthala, kukhuthala kwa zhao kotsika, kusungunuka kwakukulu, mawonekedwe osiyanasiyana a HPMC ali ndi kusiyana kwina, HPMC yosungunuka m'madzi sikhudzidwa ndi pH.
Kutentha koyaka mwadzidzidzi, kukhuthala kosasunthika, kukhuthala kwenikweni ndi kutentha kwa kusintha kwa galasi kunali 360℃, 0.341g/cm3, 1.326g/cm3 ndi 170 ~ 180℃, motsatana. Pambuyo potenthetsa, imasanduka bulauni pa 190 ~ 200 ° C ndikuyaka pa 225 ~ 230 ° C.
HPMC siisungunuka kwambiri mu chloroform, ethanol (95%), ndi diethyl ether, ndipo imasungunuka mu chisakanizo cha ethanol ndi methylene chloride, chisakanizo cha methanol ndi methylene chloride, ndi chisakanizo cha madzi ndi ethanol. Magawo ena a HPMC amasungunuka mu chisakanizo cha acetone, methylene chloride, ndi 2-propanol, komanso mu zinthu zina zachilengedwe.
Gome 1: Zizindikiro zaukadaulo
pulojekiti
Gauge,
60 gd (2910).
65GD (2906)
75GD(2208)
Methoxy %
28.0-32.0
27.0-30.0
19.0-24.0
Hydroxypropoxy %
7.0-12.0
4.0-7.5
4.0-12.0
Kutentha kwa gel ℃
56-64.
62.0-68.0
70.0-90.0
Kukhuthala kwa mpa s.
3,5,6,15,50,4000
50400 0
100400 0150 00100 000
Kuchepetsa thupi kouma %
5.0 kapena kuchepera
Zotsalira zoyaka %
1.5 kapena kuchepera
pH
4.0-8.0
Chitsulo cholemera
20 kapena kuchepera
arsenic
2.0 kapena kuchepera
2. Zinthu zomwe zili mu malonda
2.1 Hydroxypropyl methylcellulose imasungunuka m'madzi ozizira kuti ipange yankho la colloidal lokhuthala. Bola ikawonjezeredwa m'madzi ozizira ndikusunthidwa pang'ono, imatha kusungunuka kukhala yankho lowonekera. M'malo mwake, kwenikweni siisungunuka m'madzi otentha opitilira 60℃ ndipo imatha kutupa kokha. Pokonzekera yankho lamadzi la hydroxypropyl methicellulose, ndibwino kuwonjezera gawo la hydroxypropyl methicellulose mumadzi enaake, kusakaniza mwamphamvu, kutenthedwa mpaka 80 ~ 90℃, kenako onjezerani hydroxypropyl methicellulose yotsala, ndipo pomaliza gwiritsani ntchito madzi ozizira kuti muwonjezere kuchuluka komwe mukufuna.
2.2 Hydroxypropyl methylcellulose ndi ether ya cellulose yosakhala ionic, yankho lake silikhala ndi mphamvu ya ionic, siligwirizana ndi mchere wachitsulo kapena mankhwala a ionic organic, kuti zitsimikizire kuti HPMC sichitapo kanthu ndi zinthu zina zopangira ndi zinthu zina zowonjezera popanga.
2.3 Hydroxypropyl methylcellulose ili ndi anti-sensitivity yamphamvu, ndipo chifukwa cha kuchuluka kwa mamolekyulu omwe amalowa m'malo mwake, anti-sensitivity imawonjezekanso. Mankhwala omwe amagwiritsa ntchito HPMC ngati excipients amakhala ndi khalidwe lokhazikika mkati mwa nthawi yogwira ntchito kuposa mankhwala omwe amagwiritsa ntchito excipients zina zachikhalidwe (wowuma, dextrin, shuga wophwanyidwa).
2.4 Hydroxypropyl methylcellulose ndi yopanda mphamvu pa kagayidwe kachakudya. Monga chowonjezera cha mankhwala, sichimaphikidwa kapena kuyamwa, kotero sichipereka kutentha m'mankhwala ndi chakudya. Chimagwiritsidwa ntchito mwapadera pamtengo wotsika wa calorific, wopanda mchere, mankhwala osayambitsa ziwengo komanso chakudya cha odwala matenda ashuga.
2.5HPMC ndi yokhazikika pa asidi ndi maziko, koma ngati pH yapitirira 2 ~ 11 ndipo yakhudzidwa ndi kutentha kwakukulu kapena nthawi yayitali yosungira, imachepetsa kukhwima.
2.6 Hydroxypropyl methylcellulose aqueous solution imatha kupereka ntchito pamwamba, kusonyeza mphamvu zolimbitsa thupi pamwamba ndi pakati pa nkhope. Ili ndi emulsification yothandiza mu dongosolo la magawo awiri ndipo ingagwiritsidwe ntchito ngati chokhazikika komanso choteteza colloid.
2.7 Madzi a Hydroxypropyl methylcellulose ali ndi mphamvu zabwino kwambiri zopangira filimu, ndipo ndi chinthu chabwino chophikira mapiritsi ndi mapiritsi. Nembanemba yomwe imapangidwa nayo ndi yopanda utoto komanso yolimba. Ngati glycerol yowonjezeredwa, pulasitiki yake imatha kuwonjezeka. Pambuyo pokonza pamwamba, mankhwalawa amamwazika m'madzi ozizira, ndipo kuchuluka kwa kusungunuka kumatha kulamulidwa mwa kusintha pH. Amagwiritsidwa ntchito popanga zokonzekera zotulutsa pang'onopang'ono komanso zopangira zophimbidwa ndi enteric.
3. Kugwiritsa ntchito zinthu
3.1. Amagwiritsidwa ntchito ngati guluu komanso chosungunula
HPMC imagwiritsidwa ntchito polimbikitsa kusungunuka kwa mankhwala ndi kuchuluka kwa ntchito zotulutsira, imatha kusungunuka mwachindunji mu zosungunulira ngati zomatira, kukhuthala kochepa kwa HPMC kusungunuka m'madzi kuti apange njira yowonekera bwino ya colloid yomata yaminyanga, mapiritsi, mapiritsi, tinthu tating'onoting'ono pa zomatira ndi chosakaniza chosungunuka, komanso kukhuthala kwakukulu kwa guluu, komwe kumagwiritsidwa ntchito kokha chifukwa cha mitundu yosiyanasiyana ndi zofunikira zosiyanasiyana, zonse ndi 2% ~ 5%.
Njira yothetsera madzi ya HPMC ndi kuchuluka kwa ethanol kuti apange chomangira chophatikiza; Chitsanzo: Njira yothetsera madzi ya 2% HPMC yosakanizidwa ndi njira yothetsera ethanol ya 55% idagwiritsidwa ntchito popaka makapisozi a amoxicillin, kotero kuti kusungunuka kwa makapisozi a amoxicillin kwawonjezeka kuchoka pa 38% mpaka 90% popanda HPMC.
HPMC ingapangidwe ndi guluu wopangidwa ndi zinthu zosiyanasiyana zokhala ndi matope osakaniza pambuyo posungunuka; Kusungunuka kwa mapiritsi okhala ndi erythromycin enteric-coated kunawonjezeka kuchoka pa 38.26% kufika pa 97.38% pamene 2% HPMC ndi 8% starch zinaphatikizidwa.
2.2. Pangani zinthu zophikira filimu ndi zinthu zopangira filimu
HPMC monga chophimba chosungunuka m'madzi chili ndi makhalidwe awa: kukhuthala pang'ono kwa yankho; Njira yophikira ndi yosavuta; Kapangidwe kabwino kopanga filimu; Imatha kusunga mawonekedwe a chidutswacho, kulemba; Imatha kupirira chinyezi; Imatha utoto, kukoma kosintha. CHOPANGIDWACHI CHIMAGWIRITSIDWA NTCHITO NJINGA YOPHIKITSA FILIMU YOSUNUNGULIKA NDI MADZI YA MAPILO NDI MAPILO OKHALA OSAVUTA, NDIPONSO PA CHIKUTO CHA FILIMU CHOSAKHALA NDI MADZI CHOKHALA CHOVUTA KWAMBIRI, NDALAMA YOGWIRITSA NTCHITO NDI 2%-5%.
2.3, monga chowonjezera kukhuthala ndi guluu woteteza colloidal
HPMC yomwe imagwiritsidwa ntchito ngati chowonjezera mphamvu ndi 0.45% ~ 1.0%, ingagwiritsidwe ntchito ngati madontho a maso ndi chowonjezera mphamvu ya misozi; Imagwiritsidwa ntchito kulimbitsa kukhazikika kwa guluu wosagwirizana ndi madzi, kupewa kuphatikizika kwa tinthu tating'onoting'ono, komanso kupewa mvula, mlingo wamba ndi 0.5% ~ 1.5%.
2.4, monga choletsa, zinthu zotulutsa pang'onopang'ono, chotulutsira cholamulidwa komanso chotulutsira ma pore
Chitsanzo cha HPMC chokhuthala kwambiri chimagwiritsidwa ntchito kukonzekera zoletsa ndi zotulutsira zolamulidwa za mapiritsi osakanikirana a skeleton sustainable release ndi mapiritsi a hydrophilic gel skeleton sustainable release. Chitsanzo cha low-viscosity ndi chothandizira kutulutsa ma pore a mapiritsi otulutsidwa nthawi zonse kapena olamulidwa kuti mlingo woyamba wa mankhwala otere upezeke mwachangu, kutsatiridwa ndi kutulutsidwa nthawi zonse kapena kolamulidwa kuti zisunge kuchuluka koyenera m'magazi.
2.5. Gel ndi suppository matrix
Ma suppositories a hydrogel ndi zomatira za m'mimba zimatha kukonzedwa pogwiritsa ntchito mawonekedwe a hydrogel omwe amagwiritsidwa ntchito kwambiri ndi HPMC m'madzi.
2.6 Zipangizo zomatira zamoyo
Metronidazole inasakanizidwa ndi HPMC ndi polycarboxylethylene 934 mu chosakanizira kuti apange mapiritsi otulutsa olamulidwa ndi bioadhesive okhala ndi 250mg. Mayeso oyezera kusungunuka kwa mu vitro adawonetsa kuti mankhwalawa adatupa mwachangu m'madzi, ndipo kutulutsa kwa mankhwalawa kunayendetsedwa ndi kufalikira ndi kupumula kwa unyolo wa kaboni. Kukhazikitsa kwa nyama kunawonetsa kuti njira yatsopano yotulutsira mankhwala inali ndi mphamvu yayikulu yolumikizirana ndi mucosa ya ng'ombe.
2.7, monga chithandizo choyimitsa
Kukhuthala kwakukulu kwa mankhwalawa ndi njira yabwino yothandizira kuimika madzi oimika, mlingo wake wanthawi zonse ndi 0.5% ~ 1.5%.
4. Zitsanzo za ntchito
4.1 Yankho lopaka filimu: HPMC 2kg, talc 2kg, mafuta a castor 1000ml, Twain -80 1000ml, propylene glycol 1000ml, 95% ethanol 53000ml, madzi 47000ml, utoto woyenera. Pali njira ziwiri zopangira.
4.1.1 Kukonzekera zovala zothira utoto wosungunuka: Onjezani kuchuluka kwa HPMC komwe kwalembedwa mu 95% ya ethanol, mulowetseni usiku wonse, sungunulani ventricle ina ya utoto m'madzi (sefani ngati pakufunika), phatikizani mayankho awiriwa ndikusakaniza mofanana kuti mupange yankho lowonekera. Sakanizani 80% ya yankho (20% yopaka utoto) ndi kuchuluka kwa mafuta a castor, Tween-80, ndi propylene glycol komwe kwalembedwa.
4.1.2 Kukonzekera madzi osasungunuka a utoto (monga iron oxide) HPMC inanyowa mu 95% ethanol usiku wonse, ndipo madzi anawonjezedwa kuti apange yankho lowonekera la 2% HPMC. 20% ya yankho ili inachotsedwa kuti ipukutidwe, ndipo yankho lotsala la 80% ndi iron oxide zinakonzedwa pogwiritsa ntchito njira yopukutira madzi, kenako kuchuluka kwa zinthu zina zomwe zinalembedwa zinawonjezedwa ndikusakanizidwa mofanana kuti zigwiritsidwe ntchito. Njira yophikira madzi a pulasitiki: tsanulirani pepala la tirigu mu mphika wophikira shuga, mutatha kuzungulira, mpweya wotentha umatenthedwa mpaka 45℃, mutha kupopera utoto wodyetsa, kuwongolera kuyenda kwa madzi mkati mwa 10 ~ 15ml/mphindi, mutatha kupopera, pitirizani kuumitsa ndi mpweya wotentha kwa mphindi 5 ~ 10 mutha kutuluka mumphika, kuyika mu choumitsira kuti ziume kwa maola opitilira 8.
Nembanemba ya maso ya 4.2α-interferon 50μg ya α-interferon inasungunuka mu 10ml0.01ml hydrochloric acid, yosakanizidwa ndi 90ml ethanol ndi 0.5GHPMC, yosefedwa, yokutidwa ndi ndodo yozungulira yagalasi, yophikidwa pa kutentha kwa 60℃ ndikuumitsidwa mumlengalenga. Chogulitsachi chimapangidwa kukhala filimu.
Mapiritsi 4.3 a Cotrimoxazole (0.4g ± 0.08g) SMZ (maunyolo 80) 40kg, wowuma (maunyolo 120) 8kg, 3% HPMC madzi solution 18-20kg, magnesium stearate 0.3kg, TMP (maunyolo 80) 8kg, njira yokonzekera ndikusakaniza SMZ ndi TMP, kenako onjezerani wowuma ndikusakaniza kwa mphindi 5. Ndi yankho lamadzi la 3% HPMC lokonzedwa kale, zinthu zofewa, ndi ma granulation a maunyolo 16, kuumitsa, kenako ndi maunyolo 14 a maunyolo, onjezerani magnesium stearate mix, ndi mapiritsi ozungulira a 12mm okhala ndi mawu (SMZco). Chogulitsachi chimagwiritsidwa ntchito makamaka ngati chomangirira. Kusungunuka kwa mapiritsi kunali 96%/20min.
4.4 Mapiritsi a Piperate (0.25g) piperate 80 mesh 25kg, wowuma (120 mesh) 2.1kg, magnesium stearate yokwanira. Njira yake yopangira ndikusakaniza pipeoperic acid, wowuma, HPMC mofanana, ndi 20% ethanol soft material, 16 mesh screen granulate, youma, kenako 14 mesh screen whole grain, kuphatikiza vector magnesium stearate, ndi mapiritsi a 100mm circular lamba word (PPA0.25). Ndi wowuma ngati wothandizira kusweka, kuchuluka kwa kusungunuka kwa piritsili sikochepera 80%/2min, komwe kuli kokwera kuposa zinthu zofanana ku Japan.
4.5 Kung'ambika kopangidwa ndi HPMC-4000, HPMC-4500 kapena HPMC-5000 0.3g, sodium chloride 0.45g, potaziyamu chloride 0.37g, borax 0.19g, 10% ammonium chlorbenzylammonium solution 0.02ml, madzi owonjezeredwa ku 100ml. Njira yake yopangira ndi HPMC yomwe imayikidwa m'madzi a 15ml, pa 80 ~ 90℃ madzi onse, onjezerani madzi a 35ml, kenako muyikemo zinthu zina za 40ml madzi osakaniza mofanana, onjezerani madzi okwanira, kenako muyime usiku wonse, tsanulirani pang'onopang'ono kusefa, kusefa mu chidebe chotsekedwa, choyeretsedwa pa 98 ~ 100℃ kwa mphindi 30, ndiko kuti, pH imayambira 8.4 ° C mpaka 8.6 ° C. CHOPANGIDWACHI CHIMAGWIRITSIDWA NTCHITO PA SOLE YOSOWA, NDI CHOLOWA CHABWINO CHA KUSOWA, CHIKAGWIRITSIDWA NTCHITO PA MISONKHANO YA CHIPINDA CHA PAKATI, CHIMAWONJEZEREDWA MOYENERA MLINGO WA CHOPANGIDWACHI, 0.7% ~ 1.5% NDI CHOYENERA.
4.6 Mapiritsi otulutsa a Meththorphan olamulidwa ndi mchere wa meththorphan resin 187.5mg, lactose 40.0mg, PVP70.0mg, vapor silica 10mg, 40.0 mGHPMC-603, 40.0mg ~ microcrystalline cellulose phthalate-102 ndi magnesium stearate 2.5mg. Amakonzedwa ngati mapiritsi mwachizolowezi. Chogulitsachi chimagwiritsidwa ntchito ngati zinthu zotulutsira zolamulidwa.
4.7 Pa mapiritsi a avantomycin ⅳ, 2149g avantomycin ⅳ monohydrate ndi 1000ml ya madzi a isopropyl osakaniza 15% (kuchuluka kwa mass) eudragitL-100 (9:1) adasakanizidwa, kusakanizidwa, kupukutidwa, ndikuumitsidwa pa kutentha kwa 35℃. Ma granules ouma a 575g ndi 62.5g hydroxypropylocellulose E-50 adasakanizidwa bwino, kenako 7.5g stearic acid ndi 3.25g magnesium stearate adawonjezedwa ku mapiritsi kuti mapiritsi a vanguard mycin ⅳ atulutsidwe mosalekeza. Mankhwalawa amagwiritsidwa ntchito ngati zinthu zotulutsa pang'onopang'ono.
4.8 Nifedipine sulfired-release granules Gawo limodzi la nifedipine, magawo atatu a hydroxypropyl methyl cellulose ndi magawo atatu a ethyl cellulose zinasakanizidwa ndi mixed solvent (ethanol: methylene chloride = 1:1), ndipo magawo 8 a chimanga cha starch anawonjezedwa kuti apange granules pogwiritsa ntchito njira yosungunuka pang'ono. Kuchuluka kwa mankhwala otulutsidwa kwa granules sikunakhudzidwe ndi kusintha kwa pH ya chilengedwe ndipo kunali kochedwa kuposa kwa granules zomwe zimapezeka m'masitolo. Pambuyo pa maola 12 akumwa, kuchuluka kwa magazi a munthu kunali 12mg/ml, ndipo panalibe kusiyana kulikonse.
4.9 Kapisozi yotulutsa Propranhaol hydrochloride yokhazikika Propranhaol hydrochloride 60kg, microcrystalline cellulose 40kg, kuwonjezera madzi 50L kuti apange ma granules. HPMC1kg ndi EC 9kg zinasakanizidwa mu solvent yosakanikirana (methylene chloride: methanol =1:1) 200L kuti apange yankho lophimba, ndi kuthamanga kwa 750ml/min kupopera pa tinthu tozungulira tozungulira, kuphimba tinthu kudzera mu kukula kwa tinthu tating'onoting'ono ta 1.4mm screen, kenako kudzazidwa mu kapisozi yamwala ndi makina wamba odzaza kapisozi. Kapisozi iliyonse ili ndi 160mg ya tinthu tating'onoting'ono ta propranolol hydrochloride.
Mapiritsi 4.10 a Naprolol HCL opangidwa ndi mafupa anakonzedwa posakaniza naprolol HCL :HPMC: CMC-NA pa chiŵerengero cha 1:0.25:2.25. Kuchuluka kwa kutulutsidwa kwa mankhwala kunali pafupi ndi zero mkati mwa maola 12.
Mankhwala ena angapangidwenso ndi zinthu zosakaniza mafupa, monga metoprolol: HPMC: CMC-NA malinga ndi: 1:1.25:1.25; Allylprolol:HPMC malinga ndi chiŵerengero cha 1:2.8:2.92. Kuchuluka kwa kutulutsidwa kwa mankhwala kunali pafupi ndi zero mkati mwa maola 12.
4.11 Mapiritsi a mafupa a zinthu zosakaniza za ethylaminosine derivatives adakonzedwa mwachizolowezi pogwiritsa ntchito chisakanizo cha micro powder silica gel: CMC-NA :HPMC 1:0.7:4.4. Mankhwalawa akhoza kutulutsidwa kwa maola 12 onse mu vitro komanso mu vivo, ndipo mawonekedwe otulutsidwa a linear anali ndi mgwirizano wabwino. Zotsatira za mayeso okhazikika ofulumira malinga ndi malamulo a FDA zimaneneratu kuti nthawi yosungira mankhwalawa ndi zaka ziwiri.
4.12 HPMC (50mPa·s) (zigawo 5), HPMC (4000 mPa·s) (zigawo 3) ndi HPC1 zinasungunuka m'madzi 1000, magawo 60 a acetaminophen ndi magawo 6 a silica gel anawonjezedwa, anasakaniza ndi homogenizer, ndipo anaumitsa. Mankhwalawa ali ndi 80% ya mankhwala akuluakulu.
4.13 Mapiritsi a mafupa a Theophylline hydrophilic gel anawerengedwa malinga ndi kulemera kwa mapiritsi onse, 18%-35% theophylline, 7.5%-22.5% HPMC, 0.5% lactose, ndi kuchuluka koyenera kwa mafuta oletsa hydrophobic nthawi zambiri ankakonzedwa m'mapiritsi otulutsidwa bwino, omwe amatha kusunga kuchuluka kwa magazi m'thupi la munthu kwa maola 12 atatha kumwa.
Nthawi yotumizira: Sep-20-2022