I-Hydroxypropyl methylcellulose (HPMC)
Udidi: izinto zokugquma; Izinto zeMembrane; Izinto zepolymer ezilawulwa ngesantya sokulungiselela ukukhulula kancinci; Iarhente yokuzinzisa; Isixhobo sokuncedisa ukumiswa, iglu yethebhulethi; Iarhente yokuncamathelisa eqinisiweyo.
1. Intshayelelo yemveliso
Le MVELISO AYI-IONIC CELLULOSE ETHER, ebonwa ngaphandle njengomgubo omhlophe, ayinavumba kwaye ayinancasa, iyanyibilika emanzini nakwiintlaka ezininzi ze-polar organic solvents, idumba emanzini abandayo ukuya kwisisombululo se-colloidal esicacileyo okanye esifakwe i-turBId kancinci. Isisombululo samanzi sinomsebenzi womphezulu, sibonakala kakhulu kwaye sisebenza ngokuzinzileyo. I-HPMC inepropathi yejeli eshushu. Emva kokufudumeza, isisombululo samanzi semveliso senza i-gel precipitation, size sinyibilike emva kokuphola. Ubushushu bejeli beenkcukacha ezahlukeneyo buyahluka. Ukunyibilika kuyatshintsha xa i-viscosity iphantsi, kokukhona ukunyibilika kukhulu, iinkcukacha ezahlukeneyo zeempawu ze-HPMC zinezahluko ezithile, i-HPMC enyibilikisiweyo emanzini ayichaphazeleki lixabiso le-pH.
Ubushushu bokutsha obuzenzekelayo, uxinano olukhululekileyo, uxinano lokwenyani kunye nobushushu bokutshintsha kweglasi bebuyi-360℃, 0.341g/cm3, 1.326g/cm3 kunye ne-170 ~ 180℃, ngokulandelelana. Emva kokufudumeza, iba mdaka kwi-190 ~ 200 ° C kwaye itshise kwi-225 ~ 230 ° C.
I-HPMC ayinyibiliki phantse kwi-chloroform, kwi-ethanol (95%), nakwi-diethyl ether, kwaye inyibilikiswe kumxube we-ethanol kunye ne-methylene chloride, umxube we-methanol kunye ne-methylene chloride, kunye nomxube wamanzi kunye ne-ethanol. Amanye amanqanaba e-HPMC ayanyibilika kumxube we-acetone, i-methylene chloride, kunye ne-2-propanol, kunye nakwezinye izinyibilikisi zendalo.
Itheyibhile 1: Izalathi zobugcisa
iprojekthi
Igeyiji,
60 gd (2910).
65GD(2906)
75GD(2208)
I-Methoxy %
28.0-32.0
27.0-30.0
19.0-24.0
I-Hydroxypropoxy %
7.0-12.0
4.0-7.5
4.0-12.0
Ubushushu bejeli ℃
56-64.
62.0-68.0
70.0-90.0
Ukuxinana kwe-mpa s.
3,5,6,15,50,4000
50400 0
100400 0150 00100 000
Ukunciphisa umzimba owomileyo %
5.0 okanye ngaphantsi
Intsalela etshayo %
1.5 okanye ngaphantsi
pH
4.0-8.0
Intsimbi enzima
20 okanye ngaphantsi
i-arsenic
2.0 okanye ngaphantsi
2. Iimpawu zemveliso
2.1 I-Hydroxypropyl methylcellulose inyibilika emanzini abandayo ukuze yenze isisombululo se-colloidal esiqinileyo. Ukuba nje yongezwa emanzini abandayo kwaye ixutywe kancinci, inokunyibilika ibe sisisombululo esicacileyo. Ngokwahlukileyo koko, ayinyibiliki emanzini ashushu angaphezu kwama-60℃ kwaye inokudumba kuphela. Xa kulungiselelwa isisombululo samanzi se-hydroxypropyl methicellulose, kungcono ukongeza inxalenye ye-hydroxypropyl methicellulose kumlinganiselo othile wamanzi, uvuselele ngamandla, ufudumale ukuya kuma-80 ~ 90℃, uze wongeze i-hydroxypropyl methicellulose eseleyo, kwaye ekugqibeleni usebenzise amanzi abandayo ukongeza kwisixa esifunekayo.
2.2 I-Hydroxypropyl methylcellulose yi-non-ionic cellulose ether, isisombululo sayo asithwali i-ionic charge, asidibani neetyuwa zesinyithi okanye ii-ionic organic compounds, ukuqinisekisa ukuba i-HPMC ayisabelani nezinye izinto ezikrwada kunye nezinto ezincedisayo kwinkqubo yokulungiselela imveliso.
2.3 I-Hydroxypropyl methylcellulose ine-anti-sensitivity enamandla, kwaye ngokwanda kwenqanaba lokutshintshwa kwesakhiwo se-molecular, i-anti-sensitivity nayo iyaphucuka. Amayeza asebenzisa i-HPMC njenge-excipients anomgangatho ozinzileyo kwixesha elisebenzayo kunamayeza asebenzisa ezinye izinto ezincedisayo zemveli (isitatshi, i-dextrin, iswekile ecoliweyo).
2.4 I-Hydroxypropyl methylcellulose ayisebenzi ngendlela ye-metabolism. Njengesixhobo sokongeza amayeza, ayitshintshwa okanye ayifunxwa, ngoko ke ayiboneleli ngobushushu kumayeza nasekutyeni. Isebenza ngokukodwa kwixabiso eliphantsi leekhalori, amayeza angenatyuwa, angena-allergies kunye nokutya kwabantu abanesifo seswekile.
I-2.5HPMC izinzile kwi-asidi kunye neziseko, kodwa ukuba i-pH idlula i-2 ~ 11 kwaye ichaphazeleka kubushushu obuphezulu okanye ixesha elide lokugcina, iya kunciphisa izinga lokuvuthwa.
2.6 Isisombululo samanzi seHydroxypropyl methylcellulose sinokubonelela ngomsebenzi womphezulu, sibonisa amaxabiso aphakathi okuxinana komphezulu kunye noxinzelelo lwe-interfacial. Sine-emulsification esebenzayo kwinkqubo yezigaba ezimbini kwaye singasetyenziswa njengesizinzisi esisebenzayo kunye ne-colloid ekhuselayo.
2.7 Isisombululo samanzi seHydroxypropyl methylcellulose sineempawu ezintle zokwenza ifilimu, kwaye sisixhobo esihle sokugquma iipilisi kunye neepilisi. I-membrane eyenziwe yiyo ayinambala kwaye iqinile. Ukuba i-glycerol yongezwa, i-plasticity yayo inokwandiswa. Emva konyango lomphezulu, imveliso isasazeka emanzini abandayo, kwaye izinga lokunyibilika linokulawulwa ngokutshintsha imeko ye-pH. Isetyenziswa kumalungiselelo okukhululwa kancinci kunye namalungiselelo agqunywe yi-enteric.
3. Ukusetyenziswa kwemveliso
3.1. Isetyenziswa njenge-adhesive kunye ne-disintegrating agent
I-HPMC isetyenziselwa ukukhuthaza ukunyibilika kwamayeza kunye nobungakanani bokusetyenziswa kokukhululwa, inokunyibilika ngqo kwisinyibilikisi njenge-glue, i-viscosity ephantsi ye-HPMC inyibilike emanzini ukuze ibe yisisombululo se-colloid esinamathelayo se-ivory, iipilisi, iigranules kwi-glue kunye ne-arhente yokuqhekeka, kunye ne-viscosity ephezulu yeglue, isetyenziswa kuphela ngenxa yohlobo olwahlukileyo kunye neemfuno ezahlukeneyo, ngokubanzi yi-2% ~ 5%.
Isisombululo samanzi se-HPMC kunye noxinzelelo oluthile lwe-ethanol ukwenza i-composite binder; Umzekelo: Isisombululo samanzi se-2% HPMC esixutywe nesisombululo se-ethanol se-55% sisetyenziselwe ukucola ii-capsules ze-amoxicillin, ngoko ke ukunyibilika okuqhelekileyo kwee-capsules ze-amoxicillin kwanda ukusuka kwi-38% ukuya kwi-90% ngaphandle kwe-HPMC.
I-HPMC ingenziwa nge-composite adhesive ene-concentrate concentrated eyahlukileyo ye-starch slurry emva kokunyibilika; Ukunyibilika kweepilisi ezine-erythromycin enteric-coated kwanda ukusuka kwi-38.26% ukuya kwi-97.38% xa i-2% ye-HPMC kunye ne-8% ye-starch zadityaniswa.
2.2. Yenza izinto zokugquma ifilimu kunye nezinto zokwenza ifilimu
I-HPMC njengesixhobo sokugquma esinyibilikayo emanzini ineempawu ezilandelayo: ukuxinana kwesisombululo okuphakathi; Inkqubo yokugquma ilula; Ipropati entle yokwenza ifilimu; Ingagcina imilo yesiqwenga, ibhala; Ingamelana nokufuma; Inganombala, incasa yokulungisa. Le MVELISO ISETYENZISWA NJENGESIGQIBO SEFILIMU ESINXULUMEKAYO NGAMANZI KWIIPILISI NEZIPHILISI EZINOBUMBA OBUSINCI, KWAYE KWISIGQIBO SEFILIMU ESINGASETYENZISWA NGAMANZI ESINOBUMBA OBUSINCI, ISIXA-MALI SOKUSETYENZISWA YI-2%-5%.
2.3, njenge-arhente yokutyeba kunye neglu yokukhusela i-colloidal
I-HPMC esetyenziswa njenge-arhente yokutyeba yi-0.45% ~ 1.0%, ingasetyenziswa njenge-eye drops kunye ne-arhente yokutyeba iinyembezi eyenziweyo; Isetyenziselwa ukwandisa uzinzo lweglue enganyangekiyo, ukuthintela ukuhlangana kwamasuntswana, imvula, idosi eqhelekileyo yi-0.5% ~ 1.5%.
2.4, njengesithinteli, izinto ezikhupha kancinci, iarhente yokukhupha elawulwayo kunye nearhente ye-pore
Imodeli ye-HPMC high viscosity isetyenziselwa ukulungiselela ii-blockers kunye nee-release agents ezilawulwayo zeetablethi ze-skeleton sustainable release ezixutyiweyo kunye neetablethi ze-hydrophilic gel skeleton sustainable release. Imodeli ye-low-viscosity yiarhente ebangela iimbobo zeetablethi ze-sustained-release okanye ze-controlled-release ukuze idosi yokuqala yonyango lweetablethi ezinjalo ifumaneke ngokukhawuleza, ilandelwe yi-sustained-release okanye ye-controlled-release ukugcina uxinaniso olusebenzayo egazini.
2.5. Ijeli kunye ne-suppository matrix
Iisuppositories zeHydrogel kunye namalungiselelo okuncamathelisa esiswini angalungiswa ngokusebenzisa uphawu lokwakheka kwehydrogel olusetyenziswa kakhulu yiHPMC emanzini.
2.6 Izinto zokuncamathelisa zebhayoloji
I-Metronidazole ixutywe ne-HPMC kunye ne-polycarboxylethylene 934 kwi-mixer ukwenza iipilisi zokukhululwa ezilawulwa yi-bioadhesive ezine-250mg. Uvavanyo lokunyibilika kwe-in vitro lubonise ukuba olu lungiselelo lwadumba ngokukhawuleza emanzini, kwaye ukukhululwa kwamayeza kulawulwa kukusasazwa kunye nokukhululeka kwe-carbon chain. Ukusetyenziswa kwezilwanyana kubonise ukuba inkqubo entsha yokukhululwa kwamayeza yayineempawu ezibalulekileyo zokunamathela kwi-mucosa ye-bovine sublingual.
2.7, njengesixhobo sokuncedisa ukuxhoma
Ubuninzi be-viscosity yale mveliso buluncedo olukhulu ekumisweni kolwelo lokumiliswa, idosi yayo eqhelekileyo yi-0.5% ~ 1.5%.
4. Imizekelo yokusetyenziswa
4.1 Isisombululo sokugquma ifilimu: HPMC 2kg, talc 2kg, ioyile yecastor 1000ml, Twain -80 1000ml, propylene glycol 1000ml, 95% ethanol 53000ml, amanzi 47000ml, umbala ofanelekileyo. Zimbini iindlela zokwenza.
4.1.1 Ukulungiswa kolwelo olugqunywe ngemibala enyibilikayo: Yongeza ubungakanani obumiselweyo be-HPMC kwi-95% ye-ethanol, uyicwilise ubusuku bonke, unyibilikise enye i-pigment vector emanzini (hluza ukuba kuyimfuneko), dibanisa izisombululo ezibini kwaye uxube ngokulinganayo ukuze wenze isisombululo esicacileyo. Xuba i-80% yesisombululo (20% yokupolisha) kunye nobungakanani obumiselweyo be-castor oil, i-Tween-80, kunye ne-propylene glycol.
4.1.2 Ukulungiswa kolwelo lokugquma olunganyibilikiyo (njenge-iron oxide) i-HPMC ifakwe kwi-ethanol engama-95% ubusuku bonke, kwaye amanzi ongezwe ukwenza isisombululo esicacileyo se-2% HPMC. I-20% yesi sisombululo ikhutshwe ukuze ipholishwe, kwaye isisombululo esiseleyo se-80% kunye ne-iron oxide zalungiswa ngendlela yokugaya ulwelo, kwaye emva koko inani lezinye izinto ezisetyenzisiweyo zongezwa kwaye zaxutywa ngokulinganayo ukuze zisetyenziswe. Inkqubo yokugquma ulwelo lokugquma: galela iphepha lengqolowa kwimbiza yokugquma iswekile, emva kokujikeleza, umoya oshushu ushushu ukuya kwi-45℃, ungatshiza i-feeding coating, ulawulo lokuhamba kwamanzi kwi-10 ~ 15ml/min, emva kokutshiza, qhubeka ukoma ngomoya oshushu imizuzu emi-5 ~ 10 ungaphuma ebhodweni, ubeke kwi-dryer ukuze yome ngaphezulu kweeyure ezi-8.
I-membrane yeliso ye-4.2α-interferon I-50μg ye-α-interferon inyibilikiswe kwi-10ml0.01ml ye-hydrochloric acid, ixutywe ne-90ml ye-ethanol kunye ne-0.5GHPMC, yahluzwa, yagqunywa kwinduku yeglasi ejikelezayo, yacocwa kwi-60℃ yaza yomiswa emoyeni. Le mveliso yenziwe ngezinto zefilimu.
4.3 Iipilisi zeCotrimoxazole (0.4g±0.08g) SMZ (80 mesh) 40kg, isitashi (120 mesh) 8kg, 3%HPMC isisombululo samanzi 18-20kg, magnesium stearate 0.3kg, TMP (80 mesh) 8kg, indlela yokulungiselela kukuxuba iSMZ kunye neTMP, uze wongeze isitashi uze udibanise imizuzu emi-5. Ngesisombululo samanzi esenziwe kwangaphambili se-3%HPMC, izinto ezithambileyo, ezine-granulation yesikrini se-mesh ezili-16, ukomisa, uze emva koko nge-14 mesh screen whole grain, yongeza umxube we-magnesium stearate, kunye ne-12mm round kunye neepilisi ze-word (SMZco). Le mveliso isetyenziswa kakhulu njenge-binder. Ukunyibilika kweepilisi kwakuyi-96%/20min.
4.4 Iipilisi zePiperate (0.25g) iPiperate 80 mesh 25kg, iStarch (120 mesh) 2.1kg, iMagnesium stearate isixa esifanelekileyo. Indlela yayo yokwenza imveliso kukuxuba iPipeoperic acid, iStarch, iHPMC ngokulinganayo, kunye ne-20% ethanol soft material, i-16 mesh screen granulate, eyomileyo, kunye ne-14 mesh screen whole grain, kunye neVector magnesium stearate, kunye neepilisi zeStamping ze-100mm circular belt word (PPA0.25). Njengoko iStarch iyinto edityanisiweyo, izinga lokunyibilika kwale tablet alikho ngaphantsi kwe-80%/2min, elingaphezulu kuneemveliso ezifanayo eJapan.
4.5 Ikrazulo elenziweyo le-HPMC-4000, i-HPMC-4500 okanye i-HPMC-5000 0.3g, i-sodium chloride 0.45g, i-potassium chloride 0.37g, i-borax 0.19g, isisombululo se-ammonium chlorbenzylammonium se-10% 0.02ml, amanzi ongezwe kwi-100ml. Indlela yayo yokuvelisa yi-HPMC ebekwe emanzini ayi-15ml, kumanzi apheleleyo angama-80 ~ 90℃, thatha amanzi angama-35ml, uze ufake izithako eziseleyo zesisombululo samanzi esingama-40ml zixutywe ngokulinganayo, yongeza amanzi kwinani elipheleleyo, uze uxutywe ngokulinganayo, ume ubusuku bonke, galela ukucoca ngobunono, uhlambe kwisitya esivaliweyo, ucocwe kwiintsholongwane kuma-98 ~ 100℃ imizuzu engama-30, oko kukuthi, i-pH isusela kwi-8.4 ° C ukuya kwi-8.6 ° C. Le MVELISO ISETYENZISWA KWINTO YOKUNGENXA KWEENKRAWU, ILITSHA ELUNGILEYO LOKUTHABATHA I-KRAWU, XA ISETYENZISWA KWI-MICROSKOPU YEGUMBI ENGAPHAMBILI, INGUNYANISO NGOKUFANELEKILEYO. UMTHAMO WALE MVELISO, 0.7% ~ 1.5% UFANELEKILE.
Iipilisi zokukhululwa ezilawulwa yiMeththorphan ezi-4.6 ityuwa ye-resin ye-meththorphan eyi-187.5mg, i-lactose eyi-40.0mg, i-PVP70.0mg, i-vapor silica eyi-10mg, i-40.0 mGHPMC-603, i-40.0mg ~ microcrystalline cellulose phthalate-102 kunye ne-magnesium stearate eyi-2.5mg. Ilungiswa njengeepilisi ngendlela eqhelekileyo. Le mveliso isetyenziswa njengezinto zokukhululwa ezilawulwayo.
4.7 Kwiipilisi ze-avantomycin ⅳ, i-2149g ye-avantomycin ⅳ monohydrate kunye nomxube wamanzi we-isopropyl oyi-1000ml we-15% (uxinzelelo olukhulu) i-eudragitL-100 (9:1) yaxutywa, yaxutywa, yagalelwa, yaza yomiswa kwi-35℃. Iigranules ezomileyo ezingama-575g kunye ne-62.5g ye-hydroxypropylocellulose E-50 zaxutywa kakuhle, kwaza emva koko kongezwa i-7.5g ye-stearic acid kunye ne-3.25g ye-magnesium stearate kwiipilisi ukuze kufunyanwe ukukhululwa okuqhubekayo kweepilisi ze-vanguard mycin ⅳ. Le mveliso isetyenziswa njengezinto ezikhutshwa kancinci.
4.8 Iigranule zeNifedipine ezikhutshwa rhoqo Inxalenye e-1 ye-nifedipine, iinxalenye ezi-3 ze-hydroxypropyl methyl cellulose kunye neenxalenye ezi-3 ze-ethyl cellulose zixutywe ne-solvent exutyiweyo (i-ethanol: i-methylene chloride = 1:1), kwaye iinxalenye ezi-8 zesitatshi sombona zongezwa ukuvelisa iigranule ngendlela enyibilikayo phakathi. Izinga lokukhululwa kwamayeza eegranule alichaphazelekanga kukutshintsha kwe-pH yokusingqongileyo kwaye lalicotha kuneleegranule ezithengiswayo. Emva kweeyure ezili-12 zokusetyenziswa ngomlomo, uxinzelelo lwegazi lomntu lwaluyi-12mg/ml, kwaye kwakungekho mahluko ngamnye.
4.9 I-Propranhaol hydrochloride capsule eqhubekayo yokukhululwa I-Propranhaol hydrochloride 60kg, i-microcrystalline cellulose 40kg, yongeza amanzi angama-50L ukwenza ii-granules. I-HPMC1kg kunye ne-EC 9kg zixutywe kwi-solvent exutyiweyo (i-methylene chloride: methanol =1:1) 200L ukwenza isisombululo sokugquma, ngesantya sokuhamba kwe-750ml/min kwi-spherical particles eziqengqelekayo, ii-particles ezigqunyiweyo ngobukhulu bee-pore ze-1.4mm screen whole particles, zaza zazaliswa kwi-capsule yelitye ngomatshini oqhelekileyo wokuzalisa i-capsule. I-capsule nganye ine-160mg yee-propranolol hydrochloride spherical particles.
Iipilisi ze-skeleton ze-Naprolol HCL eziyi-4.10 zalungiswa ngokuxuba i-naprolol HCL :HPMC: CMC-NA kwi-ratio ye-1:0.25:2.25. Izinga lokukhululwa kwamayeza lalisondele kwi-zero kwiiyure ezili-12.
Amanye amayeza angenziwa ngezinto ezixutyiweyo zamathambo, ezifana ne-metoprolol: HPMC: CMC-NA ngokwe: 1:1.25:1.25; i-Allylprolol:HPMC ngokwe-1:2.8:2.92 ratio. Izinga lokukhululwa kwamayeza lalisondele kwi-zero order kwiiyure ezili-12.
4.11 Iipilisi ze-skeleton zezinto ezixutyiweyo ze-ethylaminosine derivatives zalungiswa ngendlela eqhelekileyo kusetyenziswa umxube we-micro powder silica gel: CMC-NA :HPMC 1:0.7:4.4. Eli yeza linokukhululwa iiyure ezili-12 kokubini kwi-vitro nakwi-vivo, kwaye ipateni yokukhululwa emgceni yayinolwalamano oluhle. Iziphumo zovavanyo lokuzinza olukhawulezileyo ngokwemigaqo ye-FDA zixela kwangaphambili ukuba ubomi bokugcinwa kwale mveliso bungafikelela kwiminyaka emi-2.
4.12 I-HPMC (50mPa·s) (iinxalenye ezi-5), i-HPMC (4000 mPa·s) (iinxalenye ezi-3) kunye ne-HPC1 zanyibilikiswa kwiindawo ezili-1000 zamanzi, kwafakwa iindawo ezingama-60 ze-acetaminophen kunye neendawo ezi-6 zejeli ye-silica, zaxutywa nge-homogenizer, zaza zomiswa nge-spray. Le mveliso iqulethe i-80% yeyeza eliphambili.
4.13 Iipilisi ze-Theophylline hydrophilic gel skeleton zibalwe ngokobunzima bepilisi iyonke, i-18%-35% theophylline, i-7.5%-22.5% HPMC, i-0.5% lactose, kunye nesixa esifanelekileyo se-hydrophobic lubricant zazilungiswa kwiipilisi zokukhululwa ezilawulwayo, ezinokugcina uxinzelelo lwegazi olusebenzayo emzimbeni womntu iiyure ezili-12 emva kokusetyenziswa ngomlomo.
Ixesha lokuthumela: Septemba-20-2022