1. Izakhiwo eziyisisekelo ze-HPMC
IHydroxypropyl methylcellulose, igama lesiNgisi yi-hydroxypropyl methylcellulose, eyaziwa nangokuthi i-HPMC.Ifomula yayo yamangqamuzana ithi C8H15O8-(C10Hl8O6)N-C8HL5O8, futhi isisindo sayo samangqamuzana silinganiselwa ku-86,000.Umkhiqizo u-semi-synthetic, uhlanganisa ingxenye ye-methyl kanye nengxenye ye-cellulose i-polyhydroxypropyl ether.Ingenziwa ngezindlela ezimbili: eyodwa iwukuphatha ibanga elifanele le-methyl cellulose nge-NaOH, bese isabela nge-propylene oxide ngaphansi kwezinga lokushisa eliphezulu nokucindezela okukhulu.Isikhathi sokuphendula kufanele sigcinwe ukuze amaqembu e-methyl kanye ne-hydroxypropyl akwazi ukuguqulwa abe ama-ether.Ifomu likhona futhi lihlanganiswe neringi ye-glucose ephelelwe amanzi emzimbeni we-cellulose ngokwezinga elidingekayo;enye iwukwelapha i-lint kakotini noma i-wood pulp fiber nge-caustic soda ukuze isabele ekutholeni i-methane chloride ne-propylene oxide, engacwengisiswa ngokwengeziwe futhi igaywe.Yenze ibe yimpushana ecolekile futhi efanayo noma ama-granules.I-HPMC iyisitshalo se-cellulose yemvelo kanye ne-excipient yezemithi ehlukahlukene enemithombo eminingi.Njengamanje isetshenziswa kabanzi ekhaya naphesheya futhi ingenye yezinto ezisiza kakhulu ezisetshenziswa emithini yomlomo.
Lo mkhiqizo umhlophe kuya komhlophe obisi, awunabuthi, awunaphunga, uyimbudumbudu noma unefibrous, impushana egeleza kalula.Izinzile ngokuqhathaniswa ngaphansi kokukhanya nomswakama.Iyanda emanzini abandayo ukuze yenze isixazululo se-milky colloidal nge-viscosity ethile, futhi i-sol-gel interconversion phenomenon kwenzeka ngenxa yokushintsha kwezinga lokushisa kwesisombululo ngokugxila okuthile.Incibilika kakhulu ku-70% ethanol noma i-dimethyl ketone, kodwa ayincibiliki ku-ethanol, i-chloroform noma i-ethoxyethane.
Inani le-pH le-hydroxypropyl methylcellulose liphakathi kuka-4.0 no-8.0, futhi linozinzo oluhle.Inani le-pH lizinzile phakathi kuka-3.0 no-11.0.Ingagcinwa ku-20°C kanye nomswakama ohlobene no-80% izinsuku eziyi-10.I-coefficient yokumunca umswakama ye-HPMC ingu-6.2%.
IHydroxypropyl methylcellulose inezinhlobo ezahlukene zemikhiqizo ngenxa yokuqukethwe okuhlukene kwamaqembu e-methoxy kanye ne-hydroxypropyl esakhiweni.Ezimweni ezithile, izinhlobo ezahlukene zemikhiqizo zine-viscosity ethile kanye nezakhiwo ezishisayo.Ukushisa kwe-gel ngakho-ke kunezindawo ezahlukene ezingasetshenziswa ngezinhloso ezahlukene.I-pharmacopoeia yezwe ngalinye inezidingo ezihlukile zemodeli nezinkulumo: I-European Pharmacopoeia isekelwe kuma-viscosities ahlukene, amazinga ahlukene okushintshanisa, amazinga okusetshenziswa kanye nezinombolo zamabanga ahlukahlukene emikhiqizo ethengiswa emakethe.Iyunithi ye-United States Pharmacopoeia yi-mPa·s, futhi amagama avamile alandelayo Sebenzisa amadijithi amane ukumela okuqukethwe kwe-hydroxypropyl methylcellulose enezinto ezihlukile nezinhlobo, njenge-hydroxypropyl methylcellulose, 2208. Amadijithi amabili okuqala amelela cishe amaphesenti yamaqembu e-methoxy, futhi amadijithi amabili okugcina amele iqembu le-hydroxyl.Iphesenti elilinganiselwe le-propyl.
2. I-HPMC incibilike endleleni yamanzi
2.1 Indlela yamanzi ashisayo
Njengoba i-hydroxypropyl cellulose ingancibiliki emanzini ashisayo, ingahlakazwa ngokulinganayo emanzini ashisayo bese ipholiswa.Izindlela ezimbili ezijwayelekile zenziwa ngale ndlela elandelayo:
(1) Faka inani elidingekayo lamanzi ashisayo esitsheni bese ushisa kuze kufike ku-70°C.Engeza umkhiqizo kancane kancane ngenkathi ugoqa kancane.Ekuqaleni, umkhiqizo untanta emanzini bese kancane kancane wenza i-slurry.
(2) Faka u-1/3 noma u-2/3 wenani elidingekayo lamanzi esitsheni bese uwushisa ufike ku-70°C ukuze uhlakaze umkhiqizo, ulungise udaka lwamanzi ashisayo, bese wengeza inani elisele lamanzi abandayo noma wengeze iqhwa. amanzi ku-slurry wamanzi ashisayo.slurry emanzini, gudluza ingxube ngemva kokupholisa.
2.2 Indlela yokuhlanganisa impuphu
Izinhlayiya zempushana zihlakazwa ngokuphelele ngokuxuba okomile ngenani elilinganayo noma elikhulu lezinye izithako eziyimpuphu bese zihlakazwa ngamanzi, lapho i-HMCS incibilika ngaphandle kokuhlangana.
3. Izinzuzo ze-HPMC
3.1 Incibilika emanzini abandayo
Incibilika emanzini abandayo angaphansi kuka-40 ℃ noma 70% ethanol, futhi empeleni ayincibiliki emanzini ashisayo angaphezu kuka-60 ℃, kodwa iyakwazi ukwenza ijeli.
3.2 Ukungangeni ngamakhemikhali
I-HPMC i-non-ionic cellulose ether.Isixazululo saso asinakho ukushaja kwe-ionic futhi asihlanganyeli nosawoti wensimbi noma izinhlanganisela eziphilayo ze-ionic.Ngakho-ke, amanye ama-excipients awasabelani nawo phakathi nenqubo yokukhiqiza yokulungiselela.
3.3 Ukuzinza
Iqinile ku-asidi ne-alkali futhi ingagcinwa isikhathi eside phakathi kwe-pH 3 kanye ne-1l ngaphandle koshintsho oluphawulekayo ku-viscosity.Izisombululo ezinamanzi ze-hydroxypropyl methylcellulose (HPMC) ziyi-antifungal futhi zigcina ukuqina okuhle kwe-viscosity ngesikhathi sokugcina isikhathi eside.Ukuzinza kwekhwalithi ye-HPMC kungcono kunezithako zendabuko (ezifana ne-dextrin, isitashi, njll.).
3.4 I-viscosity eguquguqukayo
I-viscosity derivatives ehlukene ye-HPMC ingaba ngezilinganiso ezahlukene, futhi i-viscosity yabo ingashintshwa ngokuvumelana nezidingo ukuze ihambisane nemithetho ethile futhi ibe nobuhlobo obuhle bomugqa, ngakho-ke isilinganiso singakhethwa ngokuvumelana nezidingo.
3.5 Ukungasebenzi kahle kwe-metabolic
I-HPMC ayimuncwa noma igaywe emzimbeni futhi ayinikezi ukushisa, ngakho iyisamukeli esiphephile samalungiselelo emithi.
3.6 Ezokuphepha
I-HPMC ngokuvamile ibhekwa njengento engenabuthi, engacasuli, ene-LD50 ye-5g/kg kumagundane kanye ne-5.2g/kg kumagundane.Imithamo yansuku zonke ayinabungozi kubantu.
4 Ukusetshenziswa kwe-HPMC ekulungiseni
4.1 Izinto zokumboza ifilimu nezinto zokwakha ifilimu
IHydroxypropyl methylcellulose (HPMC) isetshenziswa njengezinto zokumboza ifilimu.Amaphilisi ayo amboziwe awanazo izinzuzo ezisobala ngaphezu kwamaphilisi amboziwe endabuko njengamaphilisi afakwe ushukela ngokwemibandela yokufihla ukunambitheka nokubukeka komuthi, kodwa ubulukhuni bawo, ukonakala, kanye ne-hygroscopicity , ukuhlakazeka okubi., ukuzuza kwesisindo sokugqoka nezinye izinkomba zekhwalithi zingcono.Ibanga eliphansi le-viscosity lalo mkhiqizo lisetshenziswa njengento yokumboza ifilimu encibilikayo emanzini kumathebulethi namaphilisi, futhi ibanga le-viscosity eliphakeme lisetshenziswa njengento yokumboza ifilimu yezinhlelo ze-organic solvent.Ukugxila kuvame ukuba ngu-2.0% ~ 20%.
4.2 Njengomuntu ohlanganisayo futhi ohlukanisayo
Ibanga eliphansi le-viscosity lalo mkhiqizo lingasetshenziswa njengesihlanganisi kanye ne-disintegrant yamaphilisi, amaphilisi, nama-granules, kuyilapho izinga le-viscosity eliphezulu lingasetshenziswa kuphela njenge-binder.Umthamo uyahlukahluka kuye ngemodeli kanye nezidingo, ngokuvamile u-5% wamaphilisi e-granulation omile kanye no-2% wamaphilisi e-granulation emanzi.
4.3 Njengosizo lokumiswa
I-ejenti elengayo iyijeli e-viscous eyi-hydrophilic futhi ingasetshenziswa ukunciphisa isivinini sokumisa izinhlayiya futhi ibambelele ebusweni bezinhlayiya ukuvimbela izinhlayiya ukuthi zingahlangani zibe amabhola.Izinsiza zokumisa zidlala indima ebalulekile ekukhiqizeni ama-suspension agents.I-HPMC iyisengezo esihle kakhulu sokumiswa.Isixazululo saso esincibilikisiwe se-colloidal singanciphisa ukungezwani okuqinile kwe-liquid-solid interfacial kanye namandla amahhala ezinhlayiya ezincane eziqinile, ngaleyo ndlela kuthuthukise ukuzinza kwesistimu yokuhlakazeka kwe-heterogeneous.Lo mkhiqizo uwukulungiswa kokumiswa kwe-viscosity ephezulu okunomphumela omuhle wokumiswa, ukuhlakazeka okulula, udonga olungenanduku, kanye nezinhlayiya ezinhle ze-flocculation.Umthamo wayo ojwayelekile ngu-0.5% kuya ku-1.5%.
4.4 Njenge-ejenti engasebenzi, ekhishwa isikhathi eside kanye ne-porogen
Izinga eliphezulu le-viscosity yalo mkhiqizo lisetshenziselwa ukulungisa amaphilisi e-hydrophilic gel matrix akhishwa okuqhubekayo, amaphilisi ezinto ezixubile ze-matrix ezikhishwa okuqhubekayo ezibuyisela emuva kanye nama-ejenti akhipha okulawulwayo.Kunomphumela wokubambezela ukukhululwa kwezidakamizwa.Ukugxila kokusetshenziswa kwayo kungu-10% -80% (W/W).Amazinga e-viscosity aphansi asetshenziswa njengama-pore inducers ekwakhiweni kokukhululwa okuqhubekayo noma okulawulwayo.Amaphilisi anjalo angafinyelela ngokushesha umthamo wokuqala odingekayo ukuze kube nomphumela wokwelapha, bese ekhiqiza umphumela wokukhululwa oqhubekayo noma olawulwayo, futhi agcine ukugxila kwezidakamizwa egazini okusebenzayo emzimbeni.IHydroxypropyl methylcellulose i-hydrates emanzini ukuze yakhe ungqimba lwejeli.Indlela yokukhishwa kwezidakamizwa yamaphilisi e-matrix ikakhulukazi ihlanganisa ukusakazeka kongqimba lwejeli kanye nokuhlakazwa kongqimba lwejeli.
4.5 Ama-thickeners nama-colloid avikelayo
Uma lo mkhiqizo usetshenziswa njenge-thickener, ukugxila okuvame ukusetshenziswa ngu-0.45% ~ 1.0%.Lo mkhiqizo ungandisa futhi ukuzinza kweglue ye-hydrophobic, yakha i-colloid evikelayo, ivimbele izinhlayiya ezivela ku-agglomeration kanye ne-agglomeration, ngaleyo ndlela ivimbele ukwakheka kwezulu.Ukugxila kwayo okuvamile ngu-0.5% ~ 1.5%.
4.6 Sebenzisa njenge-capsule material
Ngokuvamile igobolondo legobolondo le-capsule lama-capsules i-gelatin.Inqubo yokukhiqiza amagobolondo e-gelatin capsule ilula, kodwa kunezinkinga kanye nezimo ezifana nokuvikeleka okungalungile emithini ezwela umswakama kanye ne-oxygen, ukunciphisa ukuchithwa kwezidakamizwa, nokulibaziseka ukuhlakazeka kwamagobolondo we-capsule ngesikhathi sokugcinwa.Ngakho-ke, i-hydroxypropyl methylcellulose isetshenziswa esikhundleni sezinto ze-capsule ekulungiseleleni ama-capsules, okuthuthukisa ukukhiqizwa, ukubumba nokusebenzisa imiphumela yama-capsules, futhi iye yakhuthazwa kabanzi ekhaya nakwamanye amazwe.
4.7 Njenge-bioadhesive
Ubuchwepheshe be-Bioadhesion busebenzisa ama-excipients anama-polymers e-bioadhesive ukunamathela ku-mucosa yezinto eziphilayo futhi kuthuthukise ukungaguquguquki nokuqina kokuxhumana phakathi kokulungiswa kanye ne-mucosa, okuvumela ukuthi umuthi ukhululwe kancane futhi uthathwe yi-mucosa ukuze ufeze izinjongo zokwelapha.Ukuze kuzuzwe inhloso yokwelashwa, okwamanje isetshenziswa kabanzi ukwelapha izifo emgodini wamakhala, i-mucosa yomlomo nezinye izingxenye zomzimba.Ubuchwepheshe be-gastrointestinal bioadhesion wuhlobo olusha lohlelo lokulethwa kwezidakamizwa olwakhiwe eminyakeni yamuva nje.Akugcini nje ukwandisa isikhathi sokuhlala kwamalungiselelo ezidakamizwa emgudwini wamathumbu, kodwa futhi kuthuthukisa ukusebenza kokuxhumana phakathi kwesidakamizwa kanye nesayithi lokumunca ulwelwesi lwamaseli futhi lushintsha ukwakheka kwe-membrane yeseli.Ukuhamba, okungukuthi, ukungena kwesidakamizwa kumaseli we-epithelial wamathumbu, ngaleyo ndlela.
Isikhathi sokuthumela: Feb-01-2024