1. Izakhiwo eziyisisekelo ze-HPMC
IHypromellose, igama eligcwele i-hydroxypropyl methylcellulose, elibizwa ngokuthi HPMC.Ifomula yayo yamangqamuzana i-C8H15O8-(C10Hl8O6)n-C8Hl5O8, futhi isisindo sayo samangqamuzana singaba ngu-86000. Lo mkhiqizo uyingxenye ye-semi-synthetic, eyingxenye ye-methyl kanye nengxenye ye-polyhydroxypropyl ether ye-cellulose.Ingakhiqizwa ngezindlela ezimbili: eyodwa ukuthi ibanga elifanele le-methyl cellulose liphathwa nge-NaOH, bese lisabela nge-propylene oxide ngaphansi kokushisa okuphezulu nokucindezela.Ifomu lixhunywe kwindandatho ye-anhydroglucose ye-cellulose, futhi ingafinyelela izinga elifanele;enye iwukwelapha i-linter kakotini noma i-wood pulp fiber nge-caustic soda, bese isabela nge-methyl chloride kanye ne-propylene oxide ngokulandelana ukuze uyithole, bese uqhubeka uyicwenga, ichotshozwe ukuze kwenziwe impushana ecolekile nefanayo noma ama-granules.I-HPMC iyinhlobonhlobo ye-cellulose yezitshalo zemvelo, futhi iyisakhi esihle kakhulu semithi, esinemithombo eminingi ehlukahlukene.Njengamanje, isetshenziswa kabanzi ekhaya naphesheya, futhi ingenye yezinsiza zemithi enezinga eliphezulu kakhulu lokusebenzisa emithini yomlomo.
Lo mkhiqizo unombala omhlophe kuya ku-milky omhlophe, awunabo ubuthi futhi awunambitheki, futhi usesimweni sempushane noma impushana ene-fibrous egeleza kalula.Iyazinza ngaphansi kokuchayeka ekukhanyeni kanye nomswakama.Ikhukhumala emanzini abandayo ukuze yenze isisombululo se-milky colloidal esimhlophe, esinezinga elithile le-viscosity, futhi isenzakalo se-sol-gel interconversion singenzeka ngenxa yokushintsha kwezinga lokushisa lokuhlushwa okuthile kwesisombululo.Incibilika kakhulu ku-70% wotshwala noma i-dimethyl ketone, futhi ngeke incibilike otshwaleni obuphelele, i-chloroform noma i-ethoxyethane.
Lapho i-pH ye-hypromellose iphakathi kuka-4.0 no-8.0, inokusimama okuhle, futhi ingaba khona ngokuzinzile lapho i-pH iphakathi kuka-3.0 no-11.0.Uma izinga lokushisa lingu-20°C futhi umswakama ohlobene ungama-80%, ugcinwa izinsuku eziyi-10.I-coefficient yokumunca umswakama ye-HPMC ingu-6.2%.
Ngenxa yokuqukethwe okuhlukile kwe-methoxy ne-hydroxypropyl esakhiweni se-hypromellose, izinhlobo ezahlukene zemikhiqizo ziye zavela.Ekugxilweni okukhethekile, izinhlobo ezahlukene zemikhiqizo zine-viscosity ethize kanye namazinga okushisa e-Thermal gelation, ngakho-ke, anezakhiwo ezahlukene futhi angasetshenziswa ngezinhloso ezahlukene.I-pharmacopoeias yamazwe ahlukahlukene inemithethonqubo ehlukene kanye nezethulo kumamodeli: i-European Pharmacopoeia, ngokusho kwamabanga ahlukahlukene we-viscosities ehlukene kanye namadigri okushintshaniswa kwemikhiqizo ethengiswa emakethe, imelwe ngamamaki kanye nezinombolo, kanti iyunithi yi-mPa. ·s;e-United States Pharmacopoeia, igama elivamile Faka amadijithi angu-4 ekugcineni ukukhombisa okuqukethwe kanye nohlobo lwengxenye ngayinye ye-hypromellose, njenge-hypromellose 2208, amadijithi amabili okuqala amelela isilinganiso sephesenti le-methoxy, kanti amadijithi amabili okugcina amelela i-hydroxypropyl. Iphesenti elilinganiselwe.
2. Indlela yokuhlakaza i-HPMC emanzini
2.1 indlela yamanzi ashisayo
Njengoba i-hypromellose ingancibiliki emanzini ashisayo, ingahlakazwa ngokufanayo emanzini ashisayo ekuqaleni, bese ipholiswa.Izindlela ezimbili ezijwayelekile zichazwa kanje:
(1) Faka inani elidingekayo lamanzi ashisayo esitsheni, bese uwushisa ufike cishe ku-70°C, kancane kancane wengeze lo mkhiqizo ngaphansi kokunyakaziswa kancane, ekuqaleni, lo mkhiqizo untanta phezu kwamanzi, bese kancane kancane wenze i-slurry, igqugquzela Pholisa udaka phansi.
(2) Faka u-1/3 noma u-2/3 wenani elidingekayo lamanzi esitsheni bese uwushisa ufike ku-70°C ukuze uhlakaze umkhiqizo ukuze ulungise udaka lwamanzi ashisayo, bese wengeza inani elisele lamanzi abandayo noma amanzi eqhwa kuze kube ama-silts amanzi ashisayo Ku-slurry, ingxube ipholile ngemva kokugubha.
2.2 Indlela yokuhlanganisa impuphu
Izinhlayiya zempushana zihlakazwa ngokugcwele ngokuxuba okomile nenani elilinganayo noma elikhulu lezinye izithako eziyimpuphu, bese zihlakazwa emanzini.Ngalesi sikhathi, i-hypromellose ingancibilika ngaphandle kwe-agglomeration.
3. Izinzuzo ze-HPMC
3.1 Ukuncibilika kwamanzi abandayo
Incibilika emanzini abandayo angaphansi kuka-40°C noma ku-70% i-ethanol, ngokuyisisekelo ayincibiliki emanzini ashisayo angaphezu kuka-60°C, kodwa ingafakwa i-gel.
3.2 Ukungangeni ngamakhemikhali
IHypromellose (HPMC) iwuhlobo lwe-non-ionic cellulose ether.Isixazululo saso asinakho ukushaja kwe-ionic futhi asihlanganyeli nosawoti wensimbi noma izinhlanganisela eziphilayo ze-ionic.Ngakho-ke, amanye ama-excipients awaphenduli nawo phakathi nenqubo yokulungiselela.
3.3 Ukuzinza
Iqinile ku-asidi ne-alkali, futhi ingagcinwa isikhathi eside phakathi kwe-pH 3 kanye ne-1l ngaphandle koshintsho olusobala ku-viscosity.Isixazululo esinamanzi se-hypromellose (HPMC) sinomphumela wokulwa nesikhutha futhi singagcina ukuqina kwe-viscosity ngesikhathi sokugcina isikhathi eside.Imithi esebenzisa i-HPMC njengabasizi inozinzo lwekhwalithi engcono kunaleyo esebenzisa izithasiselo zendabuko (ezifana ne-dextrin, isitashi, njll.).
3.4 Ukulungiswa kwe-viscosity
I-viscosity derivatives ehlukene ye-HPMC ingaxutshwa ngokuvumelana nezilinganiso ezahlukene, futhi i-viscosity yayo ingashintsha ngokuvumelana nemithetho ethile, futhi inobudlelwane obuhle bomugqa, ngakho-ke isilinganiso singakhethwa ngokuvumelana nezidingo.
3.5 Inertia ye-Metabolic
I-HPMC ayimuncwa noma igaywe emzimbeni, futhi ayinikezi ukushisa, ngakho-ke iyisisetshenziswa esiphephile sokulungiselela imithi.
3.6 Ezokuphepha
Kukholelwa ukuthi i-HPMC iyimpahla engenabuthi futhi engacasuli.Umthamo obulalayo omaphakathi wamagundane ngu-5g/kg, kanti umthamo obulalayo omaphakathi wamagundane ngu-5.2g/kg.Imithamo yansuku zonke ayinabungozi kubantu.
4. Ukusetshenziswa kwe-HPMC ekulungiseni
4.1 Njengezinto zokumboza ifilimu nezinto zokwakha ifilimu
Ukusebenzisa i-hypromellose (HPMC) njengento yethebhulethi ehlanganiswe nefilimu, uma kuqhathaniswa namaphilisi endabuko amboziwe njengamaphilisi ahlanganiswe noshukela, amaphilisi amboziwe awanazo izinzuzo ezisobala ekufihleni ukunambitheka komuthi nokubukeka, kodwa ubulukhuni nokuqina kwawo, ukumuncwa komswakama, ukuhlakazeka, ukunamathela kwesisindo somzimba kanye nezinye izinkomba zekhwalithi zingcono.Ibanga eliphansi le-viscosity lalo mkhiqizo lisetshenziswa njengento yokumboza ifilimu encibilikayo emanzini amaphilisi namaphilisi, futhi izinga le-viscosity ephezulu lisetshenziswa njengento yokumboza ifilimu yezinhlelo ze-organic solvent.I-concentration ngokuvamile i-2.0% kuya ku-20%.
4.2 Njengokuhlanganisa nokuhlukanisa
Ibanga le-viscosity eliphansi lalo mkhiqizo lingasetshenziswa njenge-binder kanye ne-disintegrant yamaphilisi, amaphilisi, nama-granules, futhi ibanga le-viscosity ephezulu lingasetshenziswa kuphela njenge-binder.Umthamo uyahlukahluka ngamamodeli ahlukene kanye nezidingo.Ngokuvamile, umthamo we-binder wamaphilisi e-granulation owomile ngu-5%, kanti umthamo we-binder kumaphilisi we-granulation omanzi ngu-2%.
4.3 Njenge-ejenti elengayo
I-ejenti elengayo into yejeli ye-viscous ene-hydrophilicity, enganciphisa isivinini sokuthuthwa kwezinhlayiya uma isetshenziswa ejentini elengayo, futhi ingaxhunywa ebusweni bezinhlayiya ukuvimbela izinhlayiya ukuthi zingahlangani futhi zishwabane zibe yibhola. .Ama-ejenti amisiwe adlala indima ebalulekile ekwenzeni ukumiswa.I-HPMC iwuhlobo oluhle kakhulu lwama-ejenti amisiwe, futhi isixazululo sayo se-colloidal esincibilikisiwe singanciphisa ukushuba kwesixhumi esibonakalayo esiwuketshezi kanye namandla amahhala ezinhlayiyeni ezincane eziqinile, ngaleyo ndlela sithuthukise ukuzinza kwesistimu yokuhlakazeka kwe-heterogeneous.Ibanga le-viscosity ephezulu yalo mkhiqizo lisetshenziswa njengendlela yokulungiswa kwamanzi okumisiwe okulungiselelwe njenge-ejenti yokumisa.Inomphumela omuhle wokumisa okwesikhashana, kulula ukuyihlakaza kabusha, ayinamatheli odongeni, futhi inezinhlayiya ezinhle ezintantayo.Umthamo ojwayelekile ngu-0.5% kuya ku-1.5%.
4.4 Njengesivimbeli, i-ejenti yokukhululwa okuqhubekayo kanye ne-ejenti ebangela izimbotshana
Ibanga le-viscosity ephezulu yalo mkhiqizo lisetshenziselwa ukulungisa amaphilisi e-hydrophilic gel matrix akhishwa ngokuqhubekayo, ama-blockers nama-ejenti akhishwayo okulawulwayo amaphilisi ezinto ezixubile ezikhishwa njalo ze-matrix, futhi kunomphumela wokubambezela ukukhululwa kwezidakamizwa.Ukusetshenziswa kwayo ukugxila ku-10% ~ 80% (W / W).Amabanga ane-viscosity ephansi asetshenziswa njengama-ejenti enza izimbotshana zokulungiselela ukukhishwa okuqhubekayo noma ukukhishwa okulawulwayo.Umthamo wokuqala odingekayo ukuze uthole umphumela wokwelapha walolu hlobo lwethebhulethi ungafinyelelwa ngokushesha, bese usebenzisa umphumela wokukhululwa okuzinzile noma olawulwayo, futhi ukugcwala kwezidakamizwa egazini kugcinwa emzimbeni .Lapho i-hypromellose ihlangana namanzi, ithela amanzi ukuze yakhe ungqimba lwejeli.Indlela yokukhishwa kwezidakamizwa kuthebhulethi ye-matrix ikakhulukazi ihlanganisa ukusakazeka kongqimba lwejeli kanye nokuguguleka kongqimba lwejeli.
4.5 Ingcina ye-Protective njenge-thickener ne-colloid
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-agglomerating kanye ne-agglomerating, ngaleyo ndlela ivimbele ukwakheka kwe-sediment, futhi ukuhlushwa kwayo okujwayelekile ngu-0.5% ~ 1.5%.
4.6 Impahla ye-Capsule yama-capsules
Ngokuvamile i-capsule shell capsule impahla ye-capsule isekelwe ku-gelatin.Inqubo yokukhiqiza igobolondo le-gelatin capsule ilula, kodwa kunezinkinga ezithile kanye nezimo ezifana nokuvikeleka okungalungile emithini ezwela umswakama kanye nomoya-mpilo, izinga eliphansi lokuchithwa kwezidakamizwa, kanye nokulibaziseka kokuhlakazeka kwegobolondo le-capsule ngesikhathi sokugcinwa.Ngakho-ke, i-hypromellose, esikhundleni sama-capsules we-gelatin, isetshenziswa ekulungiseleleni ama-capsules, okuthuthukisa ukwakheka nokusetshenziswa kwama-capsules, futhi iye yakhuthazwa kabanzi ekhaya nakwamanye amazwe.
4.7 njenge-bioadhesive
Ubuchwepheshe be-Bioadhesion, ukusetshenziswa kwezinto ezisizayo ezinama-polymers e-bioadhesive, ngokunamathela ku-mucosa yezinto eziphilayo, kuthuthukisa ukuqhubeka nokuqina kokuxhumana phakathi kokulungiswa kanye ne-mucosa, ukuze umuthi ukhululwe kancane futhi ufakwe yi-mucosa ukuze ufeze izinjongo zokwelapha.Njengamanje isetshenziswa kabanzi Isetshenziselwa ukwelapha izifo ze-nasal cavity, i-mucosa yomlomo nezinye izingxenye.Ubuchwepheshe be-gastrointestinal bioadhesion wuhlelo olusha lokulethwa kwezidakamizwa olwakhiwe eminyakeni yamuva nje.Akugcini nje ukwandisa isikhathi sokuhlala kwamalungiselelo emithi epheshaneni lesisu, kodwa futhi kuthuthukisa ukusebenza kokuxhumana phakathi komuthi kanye nolwelwesi lwamaseli endaweni yokumuncwa, ukuguqula uketshezi lwe-cell membrane, Kuthuthukise ukungena komuthi emathunjini. amaseli e-epithelial, ngaleyo ndlela athuthukise i-bioavailability yomuthi.
4.8 Njengejeli yesihloko
Njengokulungiswa okunamathelayo kwesikhumba, ijeli inochungechunge lwezinzuzo ezifana nokuphepha, ubuhle, ukuhlanza okulula, izindleko eziphansi, inqubo yokulungiselela elula, nokuhambisana okuhle nezidakamizwa.isiqondiso.
Isikhathi sokuthumela: Dec-15-2022