I-Hydroxypropyl methylcellulose (HPMC)
Isigaba: izinto zokumboza; Izinto ze-membrane; Izinto ze-polymer ezilawulwa ngesivinini zokulungiselela ukukhulula kancane; I-ejenti yokuzinzisa; Usizo lokumiswa, ingcina yethebhulethi; I-ejenti yokunamathela eqinisiwe.
1. Isingeniso somkhiqizo
Lo MKHIQIZO UNGU-NON-IONIC CELLULOSE ETHER, obonakala ngaphandle njengompuphu omhlophe, ongenaphunga futhi ongenambitheki, oncibilikayo emanzini nasezithambisweni eziningi zezinto eziphilayo ezi-polar, ovuvukala emanzini abandayo ukuze kube yisisombululo se-colloidal esicacile noma esi-turBIdized kancane. Isixazululo samanzi sinomsebenzi wobuso, ukucaca okuphezulu kanye nokusebenza okuzinzile. I-HPMC inempahla yejeli eshisayo. Ngemva kokushisa, isixazululo samanzi somkhiqizo sakha i-gel precipitation, bese sincibilika ngemva kokupholisa. Izinga lokushisa lejeli lezinhlobo ezahlukene lihlukile. Ukuncibilika kuyashintsha nge-viscosity, i-viscosity zhao iphansi, lapho ukuncibilika kukhulu, ukucaciswa okuhlukile kwezakhiwo ze-HPMC kunomehluko othile, i-HPMC encibilikisiwe emanzini ayithintwa yinani le-pH.
Izinga lokushisa lokushisa elizenzakalelayo, ubuningi obukhululekile, ubuningi beqiniso kanye nokushisa kokushintsha kwengilazi bekuyi-360℃, 0.341g/cm3, 1.326g/cm3 kanye ne-170 ~ 180℃, ngokulandelana. Ngemva kokushisa, iba nsundu ku-190 ~ 200 ° C bese isha ku-225 ~ 230 ° C.
I-HPMC cishe ayincibiliki ku-chloroform, i-ethanol (95%), kanye ne-diethyl ether, futhi incibilikiswe engxubeni ye-ethanol kanye ne-methylene chloride, ingxube ye-methanol kanye ne-methylene chloride, kanye nengxube yamanzi kanye ne-ethanol. Amanye amazinga e-HPMC ayancibilika ezingxubeni ze-acetone, i-methylene chloride, kanye ne-2-propanol, kanye nakwezinye izinyibilikisi eziphilayo.
Ithebula 1: Izinkomba zobuchwepheshe
iphrojekthi
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
Izinga lokushisa lejeli ℃
56-64.
62.0-68.0
70.0-90.0
Ukuthamba kwe-mpa s.
3,5,6,15,50,4000
50400 0
100400 0150 00100 000
Ukwehla kwesisindo okomile %
5.0 noma ngaphansi
I-% yokushisa kwezinsalela
1.5 noma ngaphansi
pH
4.0-8.0
Insimbi enamandla
20 noma ngaphansi
i-arsenic
2.0 noma ngaphansi
2. Izici zomkhiqizo
2.1 I-Hydroxypropyl methylcellulose incibilikiswa emanzini abandayo ukuze yakhe isixazululo se-colloidal esiqinile. Uma nje ingezwa emanzini abandayo futhi ivuselelwa kancane, ingancibilikiswa ibe yisisombululo esibonakalayo. Ngokuphambene nalokho, ayincibiliki emanzini ashisayo angaphezu kuka-60℃ futhi ingavuvukala kuphela. Ekulungiseleleni isixazululo samanzi se-hydroxypropyl methicellulose, kungcono ukwengeza ingxenye ye-hydroxypropyl methicellulose enanini elithile lamanzi, uvuselele ngamandla, ufudumale ku-80 ~ 90℃, bese ufaka i-hydroxypropyl methicellulose esele, bese ekugcineni usebenzisa amanzi abandayo ukuze ungeze inani elidingekayo.
2.2 I-Hydroxypropyl methylcellulose iyi-ether ye-cellulose engeyona i-ionic, isixazululo sayo asithwali i-ionic charge, asihlangani nosawoti wensimbi noma ama-organic compounds e-ionic, ukuze kuqinisekiswe ukuthi i-HPMC ayisabelani nezinye izinto zokusetshenziswa kanye nezinto ezisizayo enqubweni yokukhiqiza.
2.3 I-Hydroxypropyl methylcellulose ine-anti-sensitivity enamandla, futhi ngokwanda kwezinga lokushintsha isakhiwo sama-molecule, i-anti-sensitivity nayo iyathuthukiswa. Izidakamizwa ezisebenzisa i-HPMC njengezihlanganisi zinekhwalithi ezinzile phakathi nesikhathi esisebenzayo kunezidakamizwa ezisebenzisa ezinye izihlanganisi zendabuko (isitashi, i-dextrin, ushukela oluyimpuphu).
2.4 I-Hydroxypropyl methylcellulose ayisebenzi kahle emzimbeni. Njengesithako semithi, ayigaywa noma ayimuncwa, ngakho ayinikezi ukushisa emithini nasekudleni. Isebenza ngendlela ehlukile kwinani eliphansi lama-calorie, imithi engenasawoti, engeyona ebangela ukungezwani komzimba kanye nokudla kwabanesifo sikashukela.
I-2.5HPMC izinzile kuma-acid nama-base, kodwa uma i-pH idlula u-2 ~ 11 futhi ithintwa ukushisa okuphezulu noma isikhathi eside sokugcina, izonciphisa izinga lokuvuthwa.
2.6 Isixazululo samanzi se-hydroxypropyl methylcellulose singanikeza umsebenzi wobuso, sibonisa amanani okucindezela okuphakathi kobuso kanye nokuhlangana. Sine-emulsification ephumelelayo ohlelweni lwezigaba ezimbili futhi singasetshenziswa njengesiqinisi esisebenzayo kanye ne-colloid evikelayo.
2.7 Isixazululo samanzi se-Hydroxypropyl methylcellulose sinezakhiwo ezinhle kakhulu zokwakha ifilimu, futhi siyinto enhle yokumboza amaphilisi namaphilisi. I-membrane eyakhiwe yiyo ayinambala futhi iqinile. Uma i-glycerol ingezwa, i-plasticity yayo ingandiswa. Ngemva kokwelashwa kwendawo, umkhiqizo uhlakazeka emanzini abandayo, futhi izinga lokuncibilika lingalawulwa ngokushintsha indawo ye-pH. Isetshenziswa ekulungiseleleni ukukhululwa kancane kanye nasekulungiseleleni okumbozwe yi-enteric.
3. Isicelo somkhiqizo
3.1. Isetshenziswa njenge-adhesive kanye ne-ejenti yokuqhekeka
I-HPMC isetshenziselwa ukukhuthaza ukuncibilika kwezidakamizwa kanye nezinga lokukhishwa kwezicelo, ingancibilikiswa ngqo ku-solvent njenge-glue, i-viscosity ephansi ye-HPMC incibilikiswa emanzini ukuze yakhe isixazululo se-colloid esinamathelayo se-ivory, amaphilisi, ama-granules ku-glue kanye ne-ejenti yokuqhekeka, kanye ne-viscosity ephezulu ye-glue, esetshenziswa kuphela ngenxa yohlobo oluhlukile nezidingo ezahlukene, okuvamile kungu-2% ~ 5%.
Isixazululo samanzi se-HPMC kanye nokuhlushwa okuthile kwe-ethanol ukwenza i-composite binder; Isibonelo: Isixazululo samanzi se-2% HPMC esixutshwe nesisombululo se-ethanol esingu-55% sasetshenziswa ekufakweni kwama-capsule e-amoxicillin, ukuze ukuncibilika okumaphakathi kwama-capsule e-amoxicillin kukhuphuke kusuka ku-38% kuya ku-90% ngaphandle kwe-HPMC.
I-HPMC ingenziwa nge-composite adhesive ene-starch slurry ehlukene ngemva kokuncibilika; Ukuncibilika kwamaphilisi e-erythromycin ambozwe nge-enteric kukhuphuke kusuka ku-38.26% kuya ku-97.38% lapho kuhlanganiswa khona i-2% HPMC kanye ne-8% starch.
2.2. Yenza izinto zokumboza ifilimu kanye nezinto zokwakha ifilimu
I-HPMC njengento yokumboza encibilika emanzini inezici ezilandelayo: ukuthambekela okulinganiselwe kwesisombululo; Inqubo yokumboza ilula; Isakhiwo esihle sokwenza ifilimu; Ingagcina ukuma kwengxenye, ibhala; Ingamelana nomswakama; Ingadala umbala, ilungise ukunambitheka. Lo MKHIQIZO USETSHENZISWA NJENGESIKHUMBA SEFILM ESINQUBEKA EMANZINI SAMATHEBHULETHI NAMAPHILISI ANE-VISCOSITY EPHANSI, FUTHI NGOKUNGASEKELWANGA EMANZINI OKUNOKUTHAMBEKELA OKUPHEZULU, INANI LOKUSEBENZISA LIYI-2%-5%.
2.3, njenge-ejenti yokuqina kanye neglue yokuvikela i-colloidal
I-HPMC esetshenziswa njenge-ejenti yokujiya ingu-0.45% ~ 1.0%, ingasetshenziswa njengamaconsi amehlo kanye ne-ejenti yokujiya izinyembezi yokwenziwa; Isetshenziselwa ukwandisa ukuzinza kweglue engangeni manzi, ukuvimbela ukuhlangana kwezinhlayiya, imvula, umthamo ojwayelekile ngu-0.5% ~ 1.5%.
2.4, njengesivimbeli, izinto zokukhulula kancane, i-ejenti yokukhulula elawulwayo kanye ne-ejenti ye-pore
Imodeli ye-HPMC high viscosity isetshenziselwa ukulungiselela ama-blocker kanye nama-release agents alawulwayo amaphilisi okukhululwa kwe-skeleton sustainable material axubile kanye namaphilisi okukhululwa kwe-skeleton sustainable gel hydrophilic. Imodeli ye-low-viscosity iyi-ejenti ebangela imbobo yamaphilisi okukhululwa kwe-susstainable noma okulawulwayo ukuze umthamo wokuqala wokwelapha wamaphilisi anjalo utholakale ngokushesha, kulandelwe ukukhululwa kwe-susstainable noma okulawulwayo ukuze kugcinwe amazinga asebenzayo egazini.
2.5. Ijeli kanye ne-suppository matrix
Ama-suppositories e-hydrogel kanye namalungiselelo okunamathela esiswini angalungiswa ngokusebenzisa isici sokwakheka kwe-hydrogel esivame ukusetshenziswa yi-HPMC emanzini.
2.6 Izinto zokunamathela eziphilayo
I-Metronidazole ixutshwe ne-HPMC kanye ne-polycarboxylethylene 934 ku-mixer ukuze kwenziwe amaphilisi okukhululwa alawulwa yi-bioadhesive aqukethe ama-250mg. Ukuhlolwa kokuncibilikiswa kwe-in vitro kubonise ukuthi umuthi wavuvukala ngokushesha emanzini, futhi ukukhishwa kwemithi kulawulwa ukusabalala kanye nokukhululeka kwe-carbon chain. Ukuqaliswa kwezilwane kubonise ukuthi uhlelo olusha lokukhululwa kwemithi lwalunezimpawu ezibalulekile zokunamathela kwebhayoloji ku-mucosa ye-sublingual yezinkomo.
2.7, njengosizo lokumiswa
Ukuqina okuphezulu kwalo mkhiqizo kuyinsiza enhle yokumiswa kwamalungiselelo oketshezi lokumiswa, umthamo wawo ojwayelekile u-0.5% ~ 1.5%.
4. Izibonelo zokusetshenziswa
4.1 Isixazululo sokumboza ifilimu: I-HPMC 2kg, i-talc 2kg, uwoyela we-castor 1000ml, i-Twain -80 1000ml, i-propylene glycol 1000ml, i-95% ethanol 53000ml, amanzi 47000ml, inani elifanele lombala. Kunezindlela ezimbili zokukwenza.
4.1.1 Ukulungiswa koketshezi lwezingubo olumbozwe nge-pigment encibilikayo: Faka inani elinqunyiwe le-HPMC ku-95% ethanol, ulicwilise ubusuku bonke, ncibilikisa elinye i-pigment vector emanzini (hluza uma kudingeka), hlanganisa izixazululo ezimbili bese uvuselela ngokulinganayo ukuze wakhe isixazululo esibonakalayo. Hlanganisa u-80% wesisombululo (20% wokupholisha) nenani elinqunyiwe likawoyela we-castor, i-Tween-80, kanye ne-propylene glycol.
4.1.2 Ukulungiswa koketshezi lokumboza olunganyibiliki (njenge-iron oxide) i-HPMC yacwiliswa ku-ethanol engu-95% ubusuku bonke, kwase kungezwa amanzi ukuze kwenziwe isisombululo esicacile esingu-2% se-HPMC. 20% yalesi sixazululo yakhishwa ukuze ipholishwe, kwathi isisombululo esisele esingu-80% kanye ne-iron oxide kwalungiswa ngendlela yokugaya uketshezi, kwabe sekufakwa inani lezinye izingxenye ezibhalwe ngomuthi futhi kwaxutshwa ngokulinganayo ukuze kusetshenziswe. Inqubo yokumboza uketshezi lokumboza: thela ishidi lokusanhlamvu ebhodweni lokumboza ushukela, ngemva kokujikeleza, umoya oshisayo ushisa ku-45℃, ungafafaza i-feeding coating, ukulawula ukugeleza ku-10 ~ 15ml/min, ngemva kokufutha, qhubeka ukoma ngomoya oshisayo imizuzu emi-5 ~ 10 ingaphuma ebhodweni, ifakwe emshinini wokomisa ukuze yome isikhathi esingaphezu kwamahora angu-8.
Ulwelwesi lwamehlo oluyi-4.2α-interferon 50μg lwe-α-interferon luncibilikiswe ku-10ml0.01ml hydrochloric acid, luxutshwe ne-90ml ethanol kanye ne-0.5GHPMC, lwahlungwa, lwambozwa enduku yengilazi ejikelezayo, lwahlanzwa ku-60℃ lwabe selomiswa emoyeni. Lo mkhiqizo wenziwe ngezinto zefilimu.
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 ukuxuba i-SMZ ne-TMP, bese ufaka isitashi bese uxuba imizuzu emi-5. Ngesisombululo samanzi esenziwe kusengaphambili esingu-3% HPMC, izinto ezithambile, ezine-granulation yesikrini esingu-16 mesh, ukomisa, bese kuba ne-14 mesh screen whole grain, engeza ingxube ye-magnesium stearate, ene-12mm round enamaphilisi e-word (SMZco). Lo mkhiqizo usetshenziswa kakhulu njenge-binder. Ukuncibilika kwamaphilisi kwakungu-96%/20min.
4.4 Amaphilisi e-Piperate (0.25g) i-piperate engu-80 mesh engu-25kg, isitashi (120 mesh) engu-2.1kg, i-magnesium stearate inani elifanele. Indlela yayo yokukhiqiza ukuxuba i-pipeoperic acid, isitashi, i-HPMC ngokulinganayo, nezinto ezithambile ze-ethanol ezingu-20%, i-granulate yesikrini esingu-16 mesh, eyomile, bese kuba yi-14 mesh screen whole grain, kanye ne-vector magnesium stearate, namaphilisi okunyathela ayi-100mm circular belt word (PPA0.25). Njengoba isitashi siyinto ehlukanisayo, izinga lokuncibilika kwaleli philisi alingaphansi kuka-80%/2min, okuphakeme kunemikhiqizo efanayo eJapane.
4.5 Ukudabuka okwenziwe nge-HPMC-4000, i-HPMC-4500 noma i-HPMC-5000 0.3g, i-sodium chloride 0.45g, i-potassium chloride 0.37g, i-borax 0.19g, isixazululo se-ammonium chlorbenzylammonium esingu-10% esingu-0.02ml, amanzi angeziwe ku-100ml. Indlela yayo yokukhiqiza i-HPMC ifakwa emanzini angu-15ml, ku-80 ~ 90℃ amanzi agcwele, thatha amanzi angu-35ml, bese ufaka izingxenye ezisele zesisombululo samanzi esingu-40ml esixutshwe ngokulinganayo, engeza amanzi enanini eligcwele, bese uxuba ngokulinganayo, ume ubusuku bonke, uthele kancane ukuhlunga, ukuhlunga esitsheni esivaliwe, kuhlanzwe ku-98 ~ 100℃ imizuzu engama-30, okungukuthi, i-pH isukela ku-8.4 ° C kuya ku-8.6 ° C. Lo MKHIQIZO USETSHENZISWA NGOKUSHODA KWEZIDUBUKO, UNGUMSEBENZI OMUHLE WOKUSHINTSHA IDUBUKO, UMA USETSHENZISWA NGOKUSEBENZISA I-microscopy yegumbi ENGAPHAMBILI, ungakhushulwa NGOKUFANELE UMTHAMO WALO MKHIQIZO, u-0.7% ~ 1.5% UFANELE.
4.6 Amaphilisi okukhululwa alawulwa yi-Meththorphan usawoti we-resin we-meththorphan ongu-187.5mg, i-lactose engu-40.0mg, i-PVP70.0mg, i-vapor silica engu-10mg, i-40.0 mGHPMC-603, i-40.0mg ~ microcrystalline cellulose phthalate-102 kanye ne-magnesium stearate engu-2.5mg. Ilungiswa njengamaphilisi ngendlela evamile. Lo mkhiqizo usetshenziswa njengento yokukhululwa elawulwayo.
4.7 Kumaphilisi e-avantomycin ⅳ, ingxube yamanzi e-avantomycin ⅳ engu-2149g kanye nengxube yamanzi e-isopropyl engu-1000ml engu-15% (ukuhlushwa okukhulu) eudragitL-100 (9:1) yavuselelwa, yaxutshwa, yagoqwa, futhi yomiswa ku-35℃. Ama-granules omisiwe angu-575g kanye no-62.5g we-hydroxypropylocellulose E-50 axutshwe kahle, kwabe sekufakwa i-7.5g ye-stearic acid kanye ne-3.25g ye-magnesium stearate kumaphilisi ukuze kutholakale ukukhishwa okuqhubekayo kwamaphilisi e-vanguard mycin ⅳ. Lo mkhiqizo usetshenziswa njengento yokukhishwa kancane.
4.8 Ama-granule e-Nifedipine akhishwa njalo Ingxenye e-1 ye-nifedipine, izingxenye ezi-3 ze-hydroxypropyl methyl cellulose kanye nezingxenye ezi-3 ze-ethyl cellulose zaxutshwa ne-solvent exubile (i-ethanol: i-methylene chloride = 1:1), kanye nezingxenye ezi-8 zesitashi sommbila zanezelwa ukuze kukhiqizwe ama-granule ngendlela encibilikayo ephakathi nendawo. Izinga lokukhishwa kwemithi yama-granule alizange lithintwe ushintsho lwe-pH yemvelo futhi lalihamba kancane kunelama-granule atholakala kwezentengiselwano. Ngemva kwamahora ayi-12 okuphathwa ngomlomo, ukuhlushwa kwegazi lomuntu kwakungu-12mg/ml, futhi kwakungekho mehluko ngamunye.
4.9 I-Propranhaol hydrochloride ekhishwa njalo I-Propranhaol hydrochloride 60kg, i-microcrystalline cellulose 40kg, enezela amanzi angu-50L ukwenza ama-granules. I-HPMC1kg kanye ne-EC 9kg kuxutshwe ku-solvent exubile (i-methylene chloride: methanol =1:1) 200L ukwenza isixazululo sokumboza, ngesilinganiso sokugeleza esingu-750ml/min esifuthweni sezinhlayiya ezigoqekayo, izinhlayiya ezimboziwe ngosayizi we-pore wezinhlayiya eziphelele zesikrini esingu-1.4mm, bese zigcwaliswa ku-capsule yetshe ngomshini ojwayelekile wokugcwalisa i-capsule. I-capsule ngayinye iqukethe u-160mg wezinhlayiya ze-propranolol hydrochloride eziyindilinga.
Amaphilisi e-skeleton e-Naprolol HCL angu-4.10 alungiswa ngokuxuba i-naprolol HCL :HPMC: CMC-NA ngesilinganiso esingu-1:0.25:2.25. Izinga lokukhishwa kwemithi lalicishe libe yi-zero kungakapheli amahora ayi-12.
Eminye imithi ingenziwa ngezinto ezixubile zamathambo, njenge-metoprolol: HPMC: CMC-NA ngokwe: 1:1.25:1.25; I-Allylprolol:HPMC ngokwesilinganiso esingu-1:2.8:2.92. Izinga lokukhishwa kwemithi lalicishe libe yi-zero phakathi kwamahora ayi-12.
4.11 Amaphilisi e-skeleton ezinto ezixubile ze-ethylaminosine derivatives alungiswa ngendlela evamile kusetshenziswa ingxube ye-micro powder silica gel: CMC-NA :HPMC 1:0.7:4.4. Umuthi ungakhishwa amahora ayi-12 kokubili ku-vitro kanye naku-vivo, futhi iphethini yokukhululwa okuqondile yayinobudlelwano obuhle. Imiphumela yokuhlolwa kokuzinza okusheshayo ngokwemithetho ye-FDA ibikezela ukuthi impilo yokugcina yalo mkhiqizo ingafika eminyakeni emi-2.
4.12 I-HPMC (50mPa·s) (izingxenye ezi-5), i-HPMC (4000 mPa·s) (izingxenye ezi-3) kanye ne-HPC1 kwancibilikiswa ezingxenyeni zamanzi eziyi-1000, kwanezelwa izingxenye ezingama-60 ze-acetaminophen kanye nezingxenye ezi-6 zejeli ye-silica, kwaxutshwa nge-homogenizer, kwase komiswa ngesifutho. Lo mkhiqizo uqukethe u-80% womuthi oyinhloko.
4.13 Amaphilisi e-skeleton e-Theophylline hydrophilic gel abalwa ngokwesisindo sethebhulethi iyonke, i-18%-35% theophylline, i-7.5%-22.5% HPMC, i-0.5% lactose, kanye nenani elifanele le-hydrophobic lubricant ngokuvamile kwakulungiswa kube amaphilisi okukhululwa alawulwayo, angagcina ukuhlushwa kwegazi okusebenzayo emzimbeni womuntu amahora ayi-12 ngemuva kokuphathwa ngomlomo.
Isikhathi sokuthunyelwe: Septhemba-20-2022