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 ukuxubeka kancane kwesisombululo se-colloidal. 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
Isikali,
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
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. ukukhiqiza.
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 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 ingandiswa. 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 enamathelayo 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 NJENGOKUMHLOBO WEFIMIYA ENXLULISEKILE NGAMANZI AMATHEBULA KANYE AMAPHILISI ANE-VISCOSITY EPHANSI, 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, izinto ezikhulula 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, kulandelwa 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 kanye 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, ene-granulation yesikrini esiyimeshi engu-16, ukomiswa, bese kuba nokusanhlamvu okuphelele kwesikrini se-mesh engu-14, engeza imiksi ye-magnesium stearate, namathebulethi 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 iwukuhlanganisa i-pipeoperic acid, isitashi, i-HPMC ngokulinganayo, ne-ethanol ethambile engu-20%, i-granulate yesikrini esinemeshi engu-16, eyomile, bese kuba isikrini esinamamitha ayi-14 okusanhlamvu okuphelele, kanye ne-vector magnesium stearate, negama lebhande eliyindilinga elingu-100mm (PPA0.25) ) amaphilisi okugxiviza. Njengoba isitashi njenge-ejenti ehlakazekayo, izinga lokuchithwa 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 i-HPMC efakwe emanzini ayi-15ml, ku-80 ~ 90℃ amanzi agcwele thatha, engeza amanzi angama-35ml, bese equkethe izingxenye ezisele zesisombululo samanzi esingu-40ml esixutshwe ngokulinganayo, engeza amanzi enani eligcwele, bese exutshwa ngokulinganayo, ame ubusuku bonke. , ngobumnene uthele ukuhlunga, hlunga esitsheni esivalwe, inzalo ku-98 ~ 100 ℃ imizuzu engama-30, okusho ukuthi, I-pH isukela ku-8.4 ° C kuya ku-8.6 ° C. Lo Mkhiqizo USENZISWA EKUSHONENI IZINYEMBEZI, USHISELELA ESIHLE SEZInyembezi, UMA USENZELISWA I-microscopy ye-ANTERIOR chamber, UNGAKHULA NGOKUFANELE ISIKHALISO SALOMKHIQIZO, 0.7% ~ 1.5% OKUFANELEKILE.
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.2 Ilungiswa 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 lithintwe ukushintsha kwe-pH yemvelo futhi lalihamba kancane kunalelo lama-granules atholakala ngokuthengisa. Ngemva kwamahora angu-12 wokuphathwa ngomlomo, ukuhlushwa kwegazi lomuntu kwakungu-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 ye-micro powder silica gel: 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 kokuqina 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) ne-HPC1 zihlakazwe ezingxenyeni ezingu-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 ngokuvumelana nesisindo sethebhulethi esiphelele, 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