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 okuhlala isikhathi eside noma okulawulwayo ukuze umthamo wokuqala wokwelapha wamaphilisi anjalo utholakale ngokushesha, kulandelwe ukukhululwa okuhlala isikhathi eside 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: Feb-05-2024