Hydroxypropyl methylcellulose (HPMC)
Qaybta: alaabta daahan; Walxaha xuubabka; Qalabka polymer-ka-xawaaraha lagu xakameeyo ee loogu talagalay diyaarinta si tartiib-tartiib ah; Wakiilka xasilinta; Kaalmada joojinta, koollada kiniinka; Wakiilka adhesion ee la xoojiyay.
1. hordhaca alaabta
Alaabadani waa ETHER CELLULOSE AAN-IONIC ah, oo dibadda lagu arkay sida budo cad, ur aan ur lahayn oo aan dhadhamin, ku milmi biyaha iyo inta badan dareerayaasha organic polar, barar biyo qabow si loo nadiifiyo ama waxooga turBIdized kolloidal. Xalka aqueous wuxuu leeyahay dhaqdhaqaaqa dusha sare, daahfurnaanta sare iyo waxqabadka xasilloon. HPMC waxay leedahay hantida jel kulul. Kuleylka ka dib, xalalka aqueous-ka badeecada wuxuu sameeyaa roobka jel, ka dibna wuu milmaa ka dib qaboojinta. Heerkulka jel ee tilmaamo kala duwan ayaa ka duwan. Solubility isbedel la viscosity, viscosity zhao hooseeyo, ka weyn milanka, sifooyinka kala duwan ee guryaha HPMC leeyihiin qaar ka mid ah kala duwanaansho, HPMC kala diri biyaha ma saameeyaa qiimaha pH.
Heerkulka gubashada kediska ah, cufnaanta dabacsan, cufnaanta dhabta ah iyo heerkulka kala-guurka dhalada waxay ahaayeen 360 ℃, 0.341g/cm3, 1.326g/cm3 iyo 170 ~ 180 ℃, siday u kala horreeyaan. Kuleylka ka dib, waxay isu beddeshaa brown at 190 ~ 200 ° C waxayna ku gubtaa 225 ~ 230 ° C.
HPMC waxay ku dhowdahay inaan lagu milmi karin chloroform, ethanol (95%), iyo diethyl ether, waxaana lagu milmay isku dar ah ethanol iyo methylene chloride, isku dar ah methanol iyo methylene chloride, iyo isku dhafka biyaha iyo ethanol. Heerarka qaar ee HPMC waxay ku milmeen isku dhafka acetone, chloride methylene, iyo 2-propanol, iyo sidoo kale dareerayaasha kale ee dabiiciga ah.
Shaxda 1: Tilmaamayaasha farsamada
mashruuc
qiyaas,
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
Heerkulka jel ℃
56-64.
62.0-68.0
70.0-90.0
Viscosity mpa s.
3,5,6,15,50,4000
50400 0
100400 0150 00100 000
Miisaan qallalan %
5.0 ama ka yar
Hadhaaga gubanaya %
1.5 ama ka yar
pH
4.0-8.0
Bir culus
20 ama ka yar
arsenic
2.0 ama ka yar
2. Tilmaamaha alaabta
2.1 Hydroxypropyl methylcellulose waxa lagu milmay biyo qabow si loo sameeyo xal kolloidal viscous ah. Ilaa inta lagu daro biyo qabow oo wax yar la walaaqay, waxaa lagu milmi karaa xal hufan. Taa lidkeeda, asal ahaan waa lagu milma biyo kulul oo ka sarreeya 60 ℃ waxayna barari kartaa oo keliya. Diyaarinta hydroxypropyl methicellulose xal aqueous ah, waxaa fiican in lagu daro qayb ka mid ah hydroxypropyl methicellulose qadar gaar ah oo biyo ah, si xoog leh u walaaq, kuleyl ilaa 80 ~ 90 ℃, ka dibna ku dar inta hartay hydroxypropyl methicellulose, ugu dambeyntiina isticmaal biyo qabow si aad u kabto. ilaa inta loo baahan yahay.
2.2 Hydroxypropyl methylcellulose waa ether aan-ionic cellulose ah, xalkeedu ma qaado kharashka ionic, ma la falgalaan cusbada biraha ama xeryahooda organic ionic, si loo hubiyo in HPMC ma falcelin la alaabta ceeriin kale iyo excipients ee habka diyaarinta. wax soo saarka.
2.3 Hydroxypropyl methylcellulose waxay leedahay dareen diidmo oo xoog leh, iyo kororka shahaadada beddelka ee qaab-dhismeedka molecular, ka-hortagga xasaasiga ayaa sidoo kale la xoojiyay. Daroogooyinka loo isticmaalo HPMC sida dawooyinku waxay leeyihiin tayo xasiloon gudaha muddada waxtarka leh marka loo eego daroogooyinka la isticmaalo waxyaabaha kale ee dhaqameed ( istaarijka, dextrin, sonkorta budada ah).
2.4 Hydroxypropyl methylcellulose waa dheef-shiid kiimikaad ahaan. Dawo-qaade ahaan, lama dheefi karo ama lama nuugo, sidaas darteed ma bixiso kulaylka daawooyinka iyo cuntada. Waxay leedahay khusayn gaar ah oo ku saabsan qiimaha kalooriga hooseeya, milix la'aanta, daawooyinka aan xasaasiyadda lahayn iyo cuntada loogu talagalay dadka qaba sonkorowga.
2.5HPMC waa mid xasiloon asiidhyada iyo saldhigyada, laakiin haddii pH ay dhaafto 2 ~ 11 oo ay saamayso heerkulka sare ama wakhtiga kaydinta oo dheer, waxay yaraynaysaa heerka bislaanshaha.
2.6 Hydroxypropyl methylcellulose xal aqueous ah ayaa bixin kara dhaqdhaqaaqa dusha sare, oo muujinaya heerka dhexdhexaadka ah iyo qiyamka xiisadda wejiga. Waxay leedahay emulsification wax ku ool ah nidaamka laba-weji waxaana loo isticmaali karaa xasiliye wax ku ool ah iyo kolloid ilaalin ah.
2.7 Hydroxypropyl methylcellulose xal aqueous wuxuu leeyahay sifooyin filim samaynta heer sare ah, waana wax daahan wanaagsan oo kiniiniyada iyo kaniiniyada. Xuubka uu sameeyay waa mid aan midab lahayn oo adag. Haddii glycerol lagu daro, balaastikadiisa waa la kordhin karaa. Daaweynta dusha sare ka dib, badeecada ayaa lagu kala firdhiyaa biyo qabow, heerka kala dirida waxaa lagu xakameyn karaa iyadoo la beddelayo deegaanka pH. Waxaa loo isticmaalaa diyaarinta si tartiib tartiib ah iyo diyaarinta daboolan.
3. Codsiga alaabta
3.1. Loo isticmaalo sida koollada iyo wakiilka kala daadsan
HPMC waxaa loo isticmaalaa si kor loogu qaado kala dirida daroogada iyo heerka codsiyada sii daayo, si toos ah loo kala diri karaa in dareere sida koolo, viscosity hoose ee HPMC kala diri biyaha si ay u sameeyaan hufan si fool-maroodi xal kolloid dhegdheg, kiniiniyada, kiniiniyada, granules on koollada iyo burburay wakiilka, iyo viscosity sare ee xabagta, kaliya loo isticmaalo iyadoo ay ugu wacan tahay nooca kala duwan iyo shuruudaha kala duwan, guud ahaan waa 2% ~ 5%.
Xalka biyaha ee HPMC iyo xaddi ethanol ah si loo sameeyo xidhitaan isku dhafan; Tusaale: 2%HPMC xal aqueous ah oo lagu qasay 55% ethanol ayaa loo isticmaalay pelleting kaabsal amoxicillin, markaas celceliska kala dirida kaabsal amoxicillin ayaa kordhay min 38% ilaa 90% HPMC la'aanteed.
HPMC waxa laga samayn karaa xabag isku dhafan oo leh kala duwanaansho kala duwan oo ah dareeraha istaarijka ka dib kala diri; Kala dirida kiniinka dahaaran ee erythromycin mindhicirka ayaa kordhay min 38.26% ilaa 97.38% markii la isku daray 2% HPMC iyo 8% istaarijka.
2.2. Samee walxaha dahaarka filimada iyo walxaha samaynta filimada
HPMC sida maaddada dahaarka ee biyaha ku milma waxay leedahay sifooyinka soo socda: viscosity xal dhexdhexaad ah; Habka daahan waa mid fudud; Hanti sameynta filim wanaagsan; Wuxuu hayn karaa qaabka gabalka, isagoo qoraya; Waxay noqon kartaa mid aan qoyaan lahayn; Midab kara, dhadhan sixid Alaabtan waxa loo isticmalaa dahaarka FILMKA BIYAHA LUGHAYA EE KIniiniyada iyo kiniiniyada muuqahoodu hooseeyaan, iyo FILIMKA AAN BIYAHA KU SALAYSAN EE DAAHAWRKA MUUQAALKA SARE, Qaddarka isticmaalku waa 2%-5%.
2.3, sida wakiilka dhumuc iyo xabagta ilaalinta kolloidal
HPMC loo isticmaalo sida wakiilka dhumucdiisu waa 0.45% ~ 1.0%, waxa loo isticmaali karaa sida dhibcaha indhaha iyo wakiilka dhumucdiisuna macmal ah; Waxaa loo isticmaalaa in lagu kordhiyo xasilloonida koollada hydrophobic, ka hortagga is-waafajinta walxaha, roobabka, qiyaasta caadiga ah waa 0.5% ~ 1.5%.
2.4, sida xannibaadaha, walxaha si tartiib tartiib ah u sii daaya, wakiilka sii-deynta la kantaroolo iyo wakiilka daloolka
Qaabka viscosity-ga sare ee HPMC waxa loo isticmaalaa in lagu diyaariyo xannibayaasha iyo wakiilada sii daynta la kantaroolo ee kiniiniyada la sii daayo ee walaxda isku dhafan iyo kaniiniyada gel qalfoofka ee sii daynta joogtada ah. Qaabka viscosity-ka hooseeya waa wakiilka daloolinta ee sii-deynta joogtada ah ama kiniinnada la xakameeyey si qiyaasta daweynta bilowga ah ee kiniinnada noocan oo kale ah si degdeg ah loo helo, oo ay ku xigto sii-deynta joogtada ah ama xakamaynta-sii-deynta si loo ilaaliyo xoogga waxtarka leh ee dhiigga.
2.5. Gel iyo matrix suppository
Suppositories Hydrogel iyo diyaarinta xabagta gastric waxaa lagu diyaarin karaa iyadoo la isticmaalayo sifada samaynta hydrogel sida caadiga ah ay HPMC ku isticmaasho biyaha.
2.6 Walxaha xabagta noolaha
Metronidazole waxaa lagu qasay HPMC iyo polycarboxylethylene 934 oo ah qase si loo sameeyo kiniiniyada sii daynta la xakameeyey ee bioadhesive ka kooban 250mg. Tijaabada kala diris ee vitro waxay muujisay in diyaarinta si degdeg ah u barartay biyaha, iyo sii deynta daroogada waxaa lagu xakameynayay faafinta iyo nasashada silsiladda kaarboon. Hirgelinta xayawaanku waxay muujisay in nidaamka cusub ee dawadu uu leeyahay sifooyin ku dheggan bayooloji oo muhiim u ah xuubka hoose ee bovine.
2.7, sida gargaarka joojinta
viscosity SARE ee alaabtani waa gargaar ganaax wanaagsan oo loogu talagalay diyaarinta dareeraha hakinta, qiyaasta caadiga ah waa 0.5% ~ 1.5%.
4. Tusaalooyinka codsiga
4.1 xal daahan Film: HPMC 2kg, talc 2kg, castor oil 1000ml, Twain -80 1000ml, propylene glycol 1000ml, 95% ethanol 53000ml, biyo 47000ml, pigment qadar ku haboon. Waxaa jira laba siyaabood oo loo sameeyo.
4.1.1 Diyaarinta dareeraha dharka midabaysan ee midabaysan: Ku dar qaddarka HPMC ee loo qoondeeyay 95% ethanol, ku qoyso habeenkii, milaan vector kale oo midabka biyaha ah (shaandhayso haddii loo baahdo), isku dar labada xal oo si siman u walaaq si aad u sameysid xal hufan . Isku qas 80% ee xalka (20% ee polishing) iyo cadadka saliidda castor ee loo qoray, Tween-80, iyo propylene glycol.
4.1.2 Diyaarinta midabka aan milmi karin (sida birta oksaydhka) dareeraha dahaadhka ah ee HPMC ayaa lagu qooyay 95% ethanol habeenkii, waxaana lagu daray biyo si ay u sameeyaan 2% HPMC xal hufan. 20% ka mid ah xalkan ayaa loo soo saaray si loo nadiifiyo, 80% ee soo hadhay xal iyo oksijiinta birta waxaa lagu diyaariyey habka dareeraha ah ee dareeraha ah, ka dibna qadarka daawada ee qaybaha kale ayaa lagu daray oo la isku daray si siman si loo isticmaalo. Habka daahan ee dareeraha daahan: ku shub xaashida hadhuudhka dheriga daahan sonkorta, wareeg ka dib, hawada kulul preheats ilaa 45 ℃, waxaad ku buufin kartaa daahan quudinta, xakamaynta socodka 10 ~ 15ml / min, ka dib buufinta, sii wad inaad qallajiso. hawo kulul leh 5 ~ 10min waxay ka bixi kartaa dheriga, ku rid qalajiyaha si aad u engegto in ka badan 8 saacadood.
4.2a-interferon xuubka isha 50μg ee α-interferon ayaa lagu milmay 10ml0.01ml hydrochloric acid, oo lagu qaso 90ml ethanol iyo 0.5GHPMC, la sifeeyay, dahaarka leh ul galaas ah oo wareeg ah, jeermis dilay at 60 ℃ oo la qalajiyey hawada. Alaabtan waxaa laga sameeyay walxo filim.
4.3 Kiniinada Cotrimoxazole (0.4g± 0.08g) SMZ (80 mesh) 40kg, istaarijka (120 mesh) 8kg, 3% HPMC xal aqueous 18-20kg, magnesium stearate 0.3kg, TMP (80 mesh) 8kg, Isku qas SMZ iyo TMP, ka dibna ku dar istaarijka oo ku qas 5min. Iyadoo prefabricated 3% HPMC xal aqueous, walxo jilicsan, oo leh 16 granulation shaashadda mesh, qalajin, ka dibna leh 14 mesh screen hadhuudh dhan, ku dar isku darka magnesium stearate, oo leh 12mm wareeg ah oo leh kelmad (SMZco) kiniinnada shaabadda. Alaabtan waxaa inta badan loo isticmaalaa sida xidhe ahaan. Kala dirida kaniiniyada waxay ahayd 96%/20min.
4.4 Kiniinada Piperate (0.25g) piperate 80 mesh 25kg, istaarij (120 mesh) 2.1kg, magnesium stearate qadar ku haboon. Habka wax soo saarkeedu waa in lagu qaso aashitada pipeoperic, istaarijka, HPMC si siman, oo leh 20% ethanol walxo jilicsan, 16 mesh granulate, qalalan, ka dibna 14 mesh screen hadhuudh oo dhan, oo lagu daray vector magnesium stearate, oo leh 100mm ereyga suunka wareegga ah (PPA0.25). ) kaniiniyada shaabadeynta. Iyada oo istaarijku yahay wakiilka kala firdhisan, heerka kala dirida kiniinkani kama yarayn 80%/2min, kaas oo ka sarreeya alaabta la midka ah ee Japan.
4.5 Ilmo macmal ah HPMC-4000, HPMC-4500 ama HPMC-5000 0.3g, sodium chloride 0.45g, potassium chloride 0.37g, borax 0.19g, 10% ammonium chlorbenzylammonium xal 0.02ml, biyo lagu daray 100ml. Habka wax-soo-saarka waa HPMC waxaa lagu dhejiyaa 15ml oo biyo ah, 80 ~ 90 ℃ biyo buuxa qaado a, ku dar 35ml biyo ah, ka dibna ay ku jiraan qaybaha soo haray ee 40ml xal aqueous isku qasan si siman, ku dar biyo ilaa qadarka buuxa, ka dibna isku qasan si siman, u istaag habeen. Si tartiib ah ugu shub shaandhaynta, shaandhayso weelka shaabadaysan, jeermis-dilaaca 98 ~ 100 ℃ 30min, taas oo ah, pH waxay u dhaxaysaa 8.4 ° C ilaa 8.6 ° C. Alaabtan waxaa loo isticmaalaa ILMI LA'AAN, waa Beddel wanaagsan oo Illin ah, MARKA loo isticmaalo microscopy qolka ANTERIOR, waxa si habboon loo kordhin karaa qiyaasta alaabtan, 0.7% ~ 1.5% waa ku habboon tahay.
4.6 Meththorphan kiniinada la xakameeyey ee meththorphan resin salt 187.5mg, lactose 40.0mg, PVP70.0mg, silica uumiga 10mg, 40.0 mGHPMC-603, 40.0mg ~ microcrystalline cellulose phthalate-102. Waxa loo diyaariyaa sidii kiniin ahaan hab caadi ah. Alaabtan waxa loo istcimaalayaa sidii walxo sii dayn ah oo la xakameeyey.
4.7 Avantomycin ⅳ kiniiniyada, 2149g avantomycin ⅳ monohydrate iyo 1000ml isopropyl biyo isku dar ah 15% eudragitL-100 (9:1) waa la walaaqay, isku qasan, granulated, oo la qalajiyey at 35 ℃. Granules-ka qallalan ee 575g iyo 62.5g hydroxypropylocellulose E-50 ayaa si fiican isku qasan, ka dibna 7.5g stearic acid iyo 3.25g magnesium stearate ayaa lagu daray kiniiniyada si loo helo sii daynta joogtada ah ee kiniiniga Vanguard mycin ⅳ. Alaabtan waxa loo istcimaalaa sidii shay si tartiib ah loo sii daayay.
4.8 Nifedipine joogteyn-sii daayo granules 1 qayb nifedipine, 3 qaybood hydroxypropyl methyl cellulose iyo 3 qaybood ethyl cellulose lagu qasay dareere isku dhafan (ethanol: methylene chloride = 1: 1), iyo 8 qaybood istaarijka galleyda ayaa lagu daray si ay u soo saaraan granules by dhexdhexaad-milmi kara. habka. Heerka siideynta daroogada ee granules ma saameynin isbedelka pH-ga deegaanka oo wuu ka gaabiyey kan granules ganacsi ahaan la heli karo. Ka dib 12 saacadood oo maamulka afka ah, xoojinta dhiigga bini'aadamku waxay ahayd 12mg / ml, mana jirin farqi shakhsi ah.
4.9 Propranhaol hydrochloride sii daynta joogtada ah ee kaabsulka Propranhaol hydrochloride 60kg, microcrystalline cellulose 40kg, ku daray 50L biyo si ay u sameeyaan granules. HPMC1kg iyo EC 9kg ayaa lagu qasi jiray dareeraha isku dhafan (methylene chloride: methanol = 1: 1) 200L si loo sameeyo xalka daahan, oo leh qiyaasta qulqulka 750ml / min buufinta qaybaha wareega wareega, qaybo daboolan iyada oo loo marayo cabbirka daloolka 1.4 mm muraayadda walxaha oo dhan, ka dibna ka buuxi kaabsalka dhagaxa leh mashiinka buuxinta kaabsulka caadiga ah. Kaabsoosha kasta waxa uu ka kooban yahay 160mg of propranolol hydrochloride spherical particles.
4.10 Naprolol HCL kaniiniyada qalfoofka ayaa la diyaariyey iyadoo la isku daray naprolol HCL :HPMC: CMC-NA ee saamiga 1: 0.25: 2.25. Heerka siideynta dawadu waxay ku dhowaatay eber 12 saacadood gudahood.
Daawooyinka kale waxa kale oo laga samayn karaa walxo qalfoofka ah, sida metoprolol: HPMC: CMC-NA sida ku cad: 1:1.25:1.25; Allylprolol:HPMC iyadoo loo eegayo saamiga 1:2.8:2.92. Heerka siideynta dawadu waxay ku dhowaatay eber 12 saacadood gudahood.
4.11 Kiniinnada qalfoofka ah ee walxaha isku dhafan ee ka soo jeeda ethylaminosine waxaa lagu diyaariyey habka caadiga ah iyadoo la adeegsanayo isku-darka budada silica gel: CMC-NA: HPMC 1: 0.7: 4.4. Daawada waxaa la sii dayn karaa 12 saacadood labadaba gudaha vitro iyo in vivo, qaabka siideynta toosanna xiriir wanaagsan ayuu lahaa. Natiijooyinka tijaabada xasiloonida ee la dedejiyey marka loo eego xeerarka FDA waxay saadaaliyaan in nolosha kaydinta alaabtani ay tahay ilaa 2 sano.
4.12 HPMC (50mPa·s) (5 qaybood), HPMC (4000 mPa·s) (3 qaybood) iyo HPC1 ayaa lagu milmay 1000 qaybood oo biyo ah, 60 qaybood oo acetaminophen ah iyo 6 qaybood oo silica gel ah ayaa lagu daray, lagu walaaqay homogenizer, iyo buufin qalajiyey. Alaabtani waxay ka kooban tahay 80% daawada ugu muhiimsan.
4.13 Theophylline hydrophilic gel skeleton kaniini ayaa loo xisaabiyay iyadoo loo eegayo wadarta miisaanka kiniinka, 18% -35% theophylline, 7.5% -22.5% HPMC, 0.5% lactose, iyo qadar ku haboon saliidaha hydrophobic ayaa sida caadiga ah loo diyaariyey kiniinnada sii deynta la kantaroolo, kuwaas oo awoodi kara joogteeyaan fiirsashada dhiigga ee waxtarka leh ee jidhka bini'aadamka 12h ka dib maamulka afka.
Waqtiga boostada: Seb-20-2022