I-Hydroxypropyl methylcellulose (HPMC)
Isigaba: izinto zokugqoka;Impahla ye-membrane;Izinto ze-polymer ezilawulwa ngokushesha zokulungiselela ukukhishwa kancane;I-ejenti yokuzinzisa;Usizo lokumiswa, ingcina yethebhulethi;I-ejenti yokunamathela eqinisiwe.
1. Isingeniso somkhiqizo
Lo MKHIQIZO UYI-NON-IONIC CELLULOSE ETHER, ebonwa ngaphandle njengempushana emhlophe, engenaphunga futhi ayinambitheki, encibilika emanzini kanye nezincibilikisi eziningi eziphila ezindaweni ezishisayo, ukuvuvukala emanzini abandayo ukusula noma isixazululo se-colloidal esithuthukisiwe kancane.Isixazululo esinamanzi sinomsebenzi ongaphezulu, ukukhanya okuphezulu nokusebenza okuzinzile.I-HPMC inendawo yejeli eshisayo.Ngemuva kokushisa, isisombululo se-aqueous somkhiqizo sakha imvula ye-gel, bese siyancibilika ngemva kokupholisa.Izinga lokushisa lejeli lokucaciswa okuhlukile lihlukile.I-Solubility ishintsha nge-viscosity, i-viscosity zhao iphansi, ukuncibilika okukhulu, ukucaciswa okuhlukile kwezakhiwo ze-HPMC kunomehluko othile, i-HPMC encibilikisiwe emanzini ayithinteki ngenani le-pH.
Izinga lokushisa elizenzakalelayo, ukuminyana okuxekethile, ukuminyana kwangempela kanye nezinga lokushisa lokushintsha kwengilazi lalingu-360℃, 0.341g/cm3, 1.326g/cm3 kanye no-170 ~ 180℃, ngokulandelana.Ngemva kokushisisa, iphenduka ibe nsundu ku-190 ~ 200 ° C bese isha ku-225 ~ 230 ° C.
I-HPMC cishe ayincibiliki ku-chloroform, i-ethanol (95%), ne-diethyl ether, futhi incibilika engxubeni ye-ethanol ne-methylene chloride, ingxube ye-methanol ne-methylene chloride, nengxube yamanzi ne-ethanol.Amanye amaleveli e-HPMC ancibilika kuzingxube ze-acetone, i-methylene chloride, ne-2-propanol, kanye nakwezinye izincibilikisi eziphilayo.
Ithebula 1: Izinkomba zobuchwepheshe
iphrojekthi
Isilinganiso,
60 gd (2910).
I-65GD(2906)
I-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
Izinga lokushisa lejeli ℃
56-64.
62.0-68.0
70.0-90.0
I-viscosity mpa s.
3,5,6,15,50,4000
50400 0
100400 0150 00100 000
Ukuncipha kwesisindo okomile %
5.0 noma ngaphansi
Izinsalela ezivuthayo %
1.5 noma ngaphansi
pH
4.0-8.0
Insimbi enzima
20 noma ngaphansi
i-arsenic
2.0 noma ngaphansi
2. Izici zomkhiqizo
2.1 IHydroxypropyl methylcellulose incibilika emanzini abandayo ukuze yakhe isixazululo se-viscous colloidal.Uma nje yengezwa emanzini abandayo futhi inyakaziswa kancane, ingancibilika ibe yisisombululo esisobala.Ngokuphambene nalokho, empeleni ayincibiliki emanzini ashisayo angaphezu kuka-60 ℃ futhi ingavuvukala kuphela.Lapho kulungiswa isixazululo samanzi se-hydroxypropyl methicellulose, kungcono ukwengeza ingxenye ye-hydroxypropyl methiccellulose enanini elithile lamanzi, ugovuze ngamandla, ushiselwe ku-80 ~ 90 ℃, bese wengeza i-hydroxypropyl methicellulose esele, futhi ekugcineni usebenzise amanzi abandayo ukuze ungeze. enanini elidingekayo.
I-2.2 I-Hydroxypropyl methylcellulose iyi-ether ye-cellulose engeyona i-ionic, isixazululo sayo asithwali i-ionic charge, ayihlanganisi nosawoti wensimbi noma ama-ionic organic compounds, ukuze kuqinisekiswe ukuthi i-HPMC ayisabelani nezinye izinto zokusetshenziswa kanye ne-excipients ngesikhathi sokulungiswa. ukukhiqizwa.
I-2.3 I-Hydroxypropyl methylcellulose ine-anti-sensitivity enamandla, futhi ngokwanda kwe-substitution degree esakhiweni samangqamuzana, i-anti-sensitivity nayo iyathuthukiswa.Izidakamizwa ezisebenzisa i-HPMC njengezihlanganisi zinekhwalithi ezinzile phakathi nesikhathi esisebenzayo kunezidakamizwa ezisebenzisa ezinye izithasiselo zendabuko (isitashi, i-dextrin, ushukela oyimpuphu).
2.4 I-Hydroxypropyl methylcellulose i-inert metabolically inert.Njengomsizi wemithi, ayisetshenziswanga i-metabolized noma imuncwe, ngakho ayinikezi ukushisa emithini nasekudleni.Isebenza ngendlela eyingqayizivele enanini eliphansi le-calorific, izidakamizwa ezingenawo usawoti, ezingezona i-allergenic kanye nokudla kwabanesifo sikashukela.
I-2.5HPMC izinzile uma kuqhathaniswa nama-acid nezisekelo, kodwa uma i-pH idlula u-2 ~ 11 futhi ithintwa izinga lokushisa eliphezulu noma isikhathi eside sokulondoloza, izonciphisa izinga lokuvuthwa.
I-2.6 Isixazululo samanzi se-Hydroxypropyl methylcellulose singanikeza umsebenzi ongaphezulu, obonisa amanani aphakathi nendawo okungezwani kobuso.Ine-emulsification ephumelelayo ohlelweni lwezigaba ezimbili futhi ingasetshenziswa njenge-stabilizer ephumelelayo kanye ne-colloid evikelayo.
I-2.7 I-Hydroxypropyl methylcellulose i-aqueous solution inezinto ezinhle kakhulu zokwakha ifilimu, futhi iyinto enhle yokwemboza amaphilisi namaphilisi.Ulwelwesi olwakhiwe yilo alunambala futhi luqinile.Uma i-glycerol ingeziwe, ipulasitiki yayo ingakhuphuka.Ngemuva kokwelashwa okungaphezulu, umkhiqizo uhlakazwa emanzini abandayo, futhi izinga lokuchithwa lingalawulwa ngokushintsha imvelo ye-pH.Isetshenziselwa ukulungiswa kokukhishwa kancane kanye namalungiselelo ahlanganiswe ne-enteric.
3. Isicelo somkhiqizo
3.1.Isetshenziswa njenge-adhesive kanye ne-ejenti ehlukanisayo
I-HPMC isetshenziselwa ukukhuthaza ukuqedwa kwezidakamizwa kanye nezinga lokukhishwa kwezicelo, ingancibilika ngokuqondile ku-solvent njenge-adhesive, i-viscosity ephansi ye-HPMC encibilikisiwe emanzini ukuze yakheke obala kusixazululo se-colloid esinamathela ngophondo lwendlovu, amaphilisi, amaphilisi, ama-granules ku-adhesive futhi ahlakazeke. i-ejenti, kanye ne-viscosity ephezulu yeglue, isetshenziswa kuphela ngenxa yohlobo oluhlukile nezidingo ezahlukahlukene, okujwayelekile kungu-2% ~ 5%.
Isixazululo se-aqueous se-HPMC kanye nokuhlangana okuthile kwe-ethanol ukwenza isibophezelo esiyinhlanganisela;Isibonelo: Isixazululo esinamanzi esingu-2% se-HPMC esixutshwe nesisombululo se-ethanol esingu-55% sasetshenziselwa ukugoqa amaphilisi e-amoxicillin, ukuze ukuqedwa okumaphakathi kwamaphilisi e-amoxicillin kunyuke kusuka ku-38% kuya ku-90% ngaphandle kwe-HPMC.
I-HPMC ingenziwa nge-adhesive eyinhlanganisela ene-concentration ehlukene ye-starch slurry ngemva kokuhlakazwa;Ukuqedwa kwamaphilisi ane-erythromycin ane-enteric-coated kukhuphuke kusuka ku-38.26% kuya ku-97.38% lapho kuhlanganiswe u-2% we-HPMC no-8% wesitashi.
2.2.Yenza izinto zokumboza ifilimu nezinto zokwakha ifilimu
I-HPMC njengento yokugqoka encibilikayo emanzini inezici ezilandelayo: i-viscosity yesisombululo esilinganiselwe;Inqubo yokumboza ilula;Impahla enhle yokwenza ifilimu;Ingakwazi ukugcina ukuma kwesiqephu, ukubhala;Kungaba umswakama;Can umbala, ukulungisa ukunambitheka.Lo MKHIQIZO USETSHENZISWA NJENGEFILMILI ENCAZULISEKA MAYELANA AMATHETHETHE KANYE AMAPHILISI ANE-VISCOSITY ELIPHANSI, KANYE NAKWEFILMI ELINGASEKE NGAMANZI ENE-VISCOSITY EPHEZULU, INANI LOKUSETSHENZISWA LINGU-2%-5%.
2.3, njenge-ejenti yokuqina kanye neglue yokuvikela i-colloidal
I-HPMC esetshenziswa njenge-ejenti yokuqina ingu-0.45% ~ 1.0%, ingasetshenziswa njengamaconsi esweni kanye ne-ejenti yokwenziwa yokuqinisa izinyembezi;Isetshenziselwa ukukhulisa ukuzinza kweglue ye-hydrophobic, ukuvimbela ukuhlangana kwezinhlayiyana, imvula, umthamo ojwayelekile ngu-0.5% ~ 1.5%.
2.4, njengesivimbeli, impahla yokukhululwa kancane, i-ejenti yokukhululwa elawulwayo kanye ne-ejenti ye-pore
Imodeli ye-HPMC ye-viscosity ephezulu isetshenziselwa ukulungisa izivimbela kanye nama-ejenti okukhululwa alawulwayo amaphilisi okukhululwa okuqinile amathambo e-hydrophilic gel kanye namaphilisi okukhululwa e-hydrophilic gel.Imodeli ye-viscosity ephansi iyi-ejenti efaka imbobo yamaphilisi okukhululwa okuqhubekayo noma okulawulwayo ukuze umthamo wokuqala wokwelapha wamaphilisi anjalo utholakale ngokushesha, okulandelwa ukukhishwa okuqhubekayo noma ukukhishwa okulawulwayo ukuze kugcinwe ukugxila okusebenzayo egazini.
2.5.Ijeli kanye ne-suppository matrix
Ama-suppositories e-Hydrogel kanye namalungiselelo okunamathela esiswini angalungiswa ngokusebenzisa isici sokwakheka kwe-hydrogel evame ukusetshenziswa yi-HPMC emanzini.
2.6 Izinto ezinamathelayo zebhayoloji
I-Metronidazole yaxutshwa ne-HPMC kanye ne-polycarboxylethylene 934 ku-mixer ukwenza amaphilisi okukhululwa alawulwa yi-bioadhesive aqukethe u-250mg.Ukuhlolwa kokuqedwa kwe-in vitro kubonise ukuthi ukulungiswa kwavuvukala ngokushesha emanzini, futhi ukukhishwa kwesidakamizwa kwakulawulwa ukusabalalisa nokuphumula kwe-carbon chain.Ukuqaliswa kwezilwane kubonise ukuthi uhlelo olusha lokukhishwa kwezidakamizwa lunezakhiwo ezibalulekile zokunamathela kwe-bovine sublingual mucosa.
2.7, njengosizo lokumiswa
I-VIscosity EPHEZULU yalo mkhiqizo iwusizo oluhle lokumiswa kokulungiswa koketshezi lokumiswa, umthamo wayo ojwayelekile ngu-0.5% ~ 1.5%.
4. Izibonelo zohlelo lokusebenza
4.1 Film enamathela Isixazululo: HPMC 2kg, talc 2kg, uwoyela castor 1000ml, Twain -80 1000ml, propylene glycol 1000ml, 95% ethanol 53000ml, amanzi 47000ml, pigment inani elifanele.Kunezindlela ezimbili zokwenza.
4.1.1 Ukulungiswa koketshezi lwezingubo ezinamekwe ngombala oncibilikayo: Engeza inani elinqunyiwe le-HPMC ku-95% ethanol, cwilisa ubusuku bonke, ncibilikisa enye i-pigment vector emanzini (isihlungi uma kunesidingo), hlanganisa lezi zixazululo ezimbili bese ugovuze ngokulinganayo ukuze wenze isixazululo esisobala. .Hlanganisa i-80% yesisombululo (20% yokupholisha) nenani elinqunyiwe lamafutha e-castor, i-Tween-80, ne-propylene glycol.
4.1.2 Ukulungiswa kwe-pigment engancibiliki (njenge-iron oxide) uketshezi olunamathelayo I-HPMC yacwiliswa ku-95% ethanol ngobusuku obubodwa, futhi amanzi engezwa ukwenza isixazululo esikhanyelayo esingu-2% se-HPMC.I-20% yalesi sixazululo yakhishelwa ukupholishwa, futhi isixazululo esingu-80% esisele kanye ne-iron oxide yalungiswa ngendlela yokugaya okuwuketshezi, bese kunezelwa inani lemithi yezinye izakhi futhi lixutshwe ngokulinganayo ukuze lisetshenziswe.Inqubo yokumboza yoketshezi lokumboza: thela ishidi lokusanhlamvu ebhodweni lokumboza ushukela, ngemuva kokujikeleza, umoya oshisayo ushisa kuze kufike ku-45 ℃, ungafafaza i-feeding coating, ulawule ukugeleza ku-10 ~ 15ml / min, emva kokufafaza, uqhubeke nokoma. ngomoya oshisayo 5 ~ 10min kungaba ngaphandle ebhodweni, faka ekomeni ukuze ome isikhathi esingaphezu 8h.
I-4.2α-interferon eye membrane 50μg ye-α-interferon yachithwa ku-10ml0.01ml hydrochloric acid, exutshwe ne-90ml ethanol ne-0.5GHPMC, yahlungwa, yambozwa ngentonga yengilazi ejikelezayo, inzalo ku-60 ℃ futhi yomiswa emoyeni.Lo mkhiqizo wenziwa into yefilimu.
4.3 amaphilisi e-Cotrimoxazole (0.4g±0.08g) SMZ (80 mesh) 40kg, isitashi (120 mesh) 8kg, 3%HPMC aqueous solution 18-20kg, magnesium stearate 0.3kg, TMP (80 mesh) 8kg, indlela yokulungiselela iwukuba hlanganisa i-SMZ ne-TMP, bese wengeza isitashi bese uxuba i-5min.Ngesixazululo samanzi esingu-3% se-HPMC esakhelwe ngaphambili, into ethambile, enembudumbudu yesikrini esiyimeshi engu-16, ukomiswa, bese kuba nohlamvu oluphelele lwesikrini semeshi engu-14, engeza imiksi ye-magnesium stearate, ngamathebulethi agxiviza angu-12mm anomjikelezo wegama (SMZco).Lo mkhiqizo usetshenziswa kakhulu njenge-binder.Ukuqedwa kwamaphilisi kwaba ngu-96%/20min.
4.4 Amaphilisi e-Piperate (0.25g) piperate 80 mesh 25kg, isitashi (120 mesh) 2.1kg, magnesium stearate inani elifanele.Indlela yayo yokukhiqiza iwukuxuba i-pipeoperic acid, isitashi, i-HPMC ngokulinganayo, ne-ethanol ethambile engu-20%, i-granulate yesikrini esinemeshi engu-16, esomile, bese kuba yi-14 mesh screen whole grain, kanye ne-vector magnesium stearate, negama lebhande eliyindilinga elingu-100mm (PPA0.25) ) amaphilisi okugxiviza.Njengoba isitashi njenge-ejenti ehlakazekayo, izinga lokuqedwa kwale thebhulethi alikho ngaphansi kuka-80%/2min, eliphakeme kunemikhiqizo efanayo e-Japan.
4.5 Izinyembezi zokwenziwa HPMC-4000, HPMC-4500 noma HPMC-5000 0.3g, sodium chloride 0.45g, potassium chloride 0.37g, borax 0.19g, 10% ammonium chlorbenzylammonium isixazululo 0.02ml 0.Indlela yokukhiqiza yayo yi-HPMC efakwe emanzini ayi-15ml, ku-80 ~ 90℃ amanzi agcwele athathe, engeza amanzi angama-35ml, bese equkethe izingxenye ezisele zesixazululo samanzi esingu-40ml esixutshwe ngokulinganayo, engeza amanzi enani eligcwele, bese exutshwa ngokulinganayo, ame ubusuku bonke. , uthele ngomusa ukuhlunga, cwenga esitsheni esivalwe, sifakwe inzalo ku-98 ~ 100℃ imizuzu engu-30, okungukuthi, I-pH isukela ku-8.4 ° C kuya ku-8.6 ° C. Lo Mkhiqizo USENZISELWA UKUNGAPHUMELELI IZINYEMBEZI, UFANELE EKHUNDLENI ELIHLE LEZINYEMBEZI, LAPHO isetshenziselwa i-microscopy yegumbi ANGAPHAMBILI, INGAKHULISA NGOKUFANELE ISIKOLO SALO MKHIQIZO, 0.7% ~ 1.5% OKUFANELE.
4.6 amaphilisi okukhishwa alawulwa yi-Meththorphan e-meththorphan resin salt 187.5mg, lactose 40.0mg, PVP70.0mg, vapor silica 10mg, 40.0 mGHPMC-603, 40.0mg ~ microcrystalline cellulose phthalate-102 ne-magnesium stemga.2Ilungiswa njengamaphilisi ngendlela evamile.Lo mkhiqizo usetshenziswa njengento yokukhululwa elawulwayo.
4.7 Kumaphilisi e-avantomycin ⅳ, 2149g avantomycin ⅳ monohydrate kanye nengxube yamanzi ye-isopropyl engu-1000ml engu-15% (i-mass concentration) i-eudragitL-100 (9:1) ashukunyiswa, axutshwa, agaywa, futhi omiswa ku-35℃.Ama-granules omisiwe angu-575g kanye ne-62.5g hydroxypropylocellulose E-50 axutshwe kahle, kwase kuthi u-7.5g stearic acid kanye ne-3.25g magnesium stearate kwengezwa kumaphilisi ukuze kutholwe ukukhishwa okuqhubekayo kwamaphilisi anguard mycin ⅳ.Lo mkhiqizo usetshenziswa njengento ekhishwa kancane.
I-4.8 I-Nifedipine-release-release granules 1 ingxenye ye-nifedipine, izingxenye ezi-3 ze-hydroxypropyl methyl cellulose kanye nezingxenye ezi-3 ze-ethyl cellulose zixutshwe ne-solvent exubile (i-ethanol: i-methylene chloride = 1: 1), kanye nezingxenye ezingu-8 zesitashi sombila zengezwe ukuze kukhiqizwe ama-granules ngokuncibilika okuphakathi. indlela.Izinga lokukhishwa kwezidakamizwa lama-granules alizange lithinteke ngokushintsha kwe-pH yemvelo futhi lalihamba kancane kunalelo lama-granules atholakala ngokuthengisa.Ngemva kwamahora angu-12 wokuphathwa ngomlomo, ukuhlushwa kwegazi lomuntu kwakungama-12mg/ml, futhi kwakungekho mehluko womuntu ngamunye.
I-4.9 Propranhaol hydrochloride i-capsule yokukhululwa okuqhubekayo i-Propranhaol hydrochloride 60kg, i-microcrystalline cellulose 40kg, yengeza amanzi angu-50L ukwenza ama-granules.I-HPMC1kg ne-EC 9kg zixutshwe kusinyibilikisi esixubile (methylene chloride: methanol =1:1) 200L ukwenza isixazululo sokumboza, nesilinganiso sokugeleza esingu-750ml/min sifuthwe ezinhlayiyeni eziyindilinga ezigoqekayo, izinhlayiya ezimboziwe ngosayizi wembotshana ongu-1.4 mm izinhlayiya eziphelele zesikrini, bese igcwaliswa ku-capsule yetshe ngomshini ojwayelekile wokugcwalisa i-capsule.I-capsule ngayinye iqukethe i-160mg yezinhlayiya eziyindilinga ze-propranolol hydrochloride.
4.10 Amaphilisi ohlaka lwe-Naprolol HCL alungiswa ngokuxuba i-naprolol HCL :HPMC: CMC-NA ngesilinganiso esingu-1:0.25:2.25.Izinga lokukhishwa kwezidakamizwa laliseduze ne-oda elinguziro phakathi namahora angu-12.
Ezinye izidakamizwa zingenziwa futhi ngezinto ezixubile zamathambo, njenge-metoprolol: HPMC: CMC-NA ngokusho: 1:1.25:1.25;I-Allylprolol :HPMC ngokwesilinganiso esingu-1:2.8:2.92.Izinga lokukhishwa kwezidakamizwa laliseduze ne-oda elinguziro phakathi namahora angu-12.
4.11 Amaphilisi amathambo ezinto ezixubile zokuphuma kwe-ethylaminosine alungiswa ngendlela evamile kusetshenziswa ingxube yejeli ye-silica eyimpuphu encane: CMC-NA :HPMC 1:0.7:4.4.Umuthi ungakhululwa amahora angu-12 kokubili ku-vitro kanye ne-vivo, futhi iphethini yokukhishwa komugqa ibe nokuhlobana okuhle.Imiphumela yokuhlolwa kokuzinza okusheshisiwe ngokwemithetho ye-FDA ibikezela ukuthi isikhathi sokugcina salo mkhiqizo singafika eminyakeni emi-2.
I-4.12 HPMC (50mPa·s) (izingxenye ezi-5), i-HPMC (4000 mPa·s) (izingxenye ezi-3) kanye ne-HPC1 zihlakazwe ezingxenyeni eziyi-1000 zamanzi, izingxenye ezingu-60 ze-acetaminophen kanye nezingxenye ezingu-6 zejeli ye-silica zanezelwa, zaxutshwa nge-homogenizer, futhi fafaza omisiwe.Lo mkhiqizo uqukethe u-80% wemithi eyinhloko.
4.13 Amaphilisi e-Theophylline hydrophilic gel skeleton tablet abalwa ngokwesisindo sethebhulethi, 18% -35% theophylline, 7.5% -22.5% HPMC, 0.5% lactose, kanye nenani elifanele le-hydrophobic lubricant lalivame ukulungiselelwa amaphilisi okukhululwa okulawulwayo, okungenzeka gcina ukugcwala kwegazi okusebenzayo komzimba womuntu amahora ayi-12 ngemuva kokuphathwa ngomlomo.
Isikhathi sokuthumela: Sep-20-2022