1. Uhlobo oluyisisekelo lwe-HPMC
I-Hypromellose, igama lesiNgisi elithi hydroxypropyl methylcellulose, elibizwa nangokuthi i-HPMC. Ifomula yayo yama-molecule yi-C8H15O8-(C10Hl8O6)n-C8Hl5O8, kanti isisindo sama-molecule singaba ngu-86,000. Lo mkhiqizo uyinto eyenziwe kancane, eyingxenye yeqembu le-methyl kanye nengxenye ye-polyhydroxypropyl ether ye-cellulose. Ingakhiqizwa ngezindlela ezimbili: eyodwa ukwelapha i-methyl cellulose yezinga elifanele nge-NaOH, bese isabela nge-propylene oxide ngaphansi kokushisa okuphezulu kanye nokucindezela okuphezulu. Isikhathi sokuphendula kumele siqhubeke ukuze kuvunyelwe amaqembu e-methyl kanye ne-hydroxypropyl ukuthi ahlangane ne-ether. Uhlobo lwe- luxhunywe endandatho ye-anhydroglucose ye-cellulose, futhi lungafinyelela izinga elifunekayo; olunye ukwelapha i-cotton linter noma i-wood pulp fiber nge-caustic soda, bese itholakala ngokuphendula nge-chlorinated methane kanye ne-propylene oxide ngokulandelana, bese ihlungwa kabanzi, i-Pulverize, yenze ibe yi-powder noma i-granule ecolekile nefanayo. I-HPMC iyinhlobonhlobo ye-cellulose yezitshalo zemvelo, futhi iyisithako esihle kakhulu semithi, esinomthombo obanzi. Njengamanje, isetshenziswa kabanzi ekhaya nakwamanye amazwe, futhi ingenye yezithako zemithi ezinesilinganiso esiphezulu sokusetshenziswa phakathi kwemithi ephuzwayo.
Umbala walo mkhiqizo umhlophe kuya komhlophe onjengobisi, awunabo ubuthi futhi awunambitheki, futhi uyimpuphu e-granular noma ene-fibrous, egeleza kalula. Izinzile uma iboniswa ukukhanya kanye nomswakama. Ivuvukala emanzini abandayo ukuze yakhe isixazululo se-colloidal esimhlophe esinjengobisi esinezinga elithile le-viscosity. Isenzakalo sokuguqulwa kwe-sol-gel singenzeka ngenxa yokushintsha kwezinga lokushisa kwengxube ethile yesisombululo. Kulula kakhulu ukuncibilikisa ku-70% alcohol noma i-dimethyl ketone, futhi ngeke incibilike ku-anhydrous alcohol, i-chloroform noma i-ethoxyethane.
I-Hypromellose inokuqina okuhle uma i-pH iphakathi kuka-4.0 no-8.0, futhi ingaba khona ngokuzinzile phakathi kuka-3.0 no-11.0. Ngemva kokugcinwa izinsuku eziyi-10 ekushiseni okungu-20°C kanye nomswakama ohlobene ongu-80%, i-HPMC iyakwazi ukumunca umswakama ongu-6.2%.
Ngenxa yomehluko wokuqukethwe kwezinto ezimbili ezithatha indawo esakhiweni se-hypromellose, i-methoxy kanye ne-hydroxypropyl, kuye kwavela izinhlobo ezahlukene zemikhiqizo. Ekugxilweni okuthile, izinhlobo ezahlukene zemikhiqizo zine-viscosity ethile kanye nokushisa kwe-Thermal gelation, ngakho-ke, kunezakhiwo ezahlukene futhi kungasetshenziswa ngezinhloso ezahlukene. Ama-pharmacopoeia amazwe ahlukahlukene anezincazelo ezahlukene kanye nezinkulumo zemodeli: I-European Pharmacopoeia isekelwe kumazinga ahlukahlukene e-viscosities ehlukene kanye namazinga ahlukene okushintshaniswa kwemikhiqizo emakethe. Ivezwa yibanga kanye nenombolo. Iyunithi yi-mPa•s. Ngemva kokwengeza izinombolo ezi-4 ukukhombisa okuqukethwe kanye nohlobo lwesithako ngasinye se-hypromellose, isibonelo, i-hypromellose 2208, izinombolo ezimbili zokuqala zimelela iphesenti elilinganiselwe leqembu le-methoxy, izinombolo ezimbili zokugcina zimelela i-hydroxypropyl Iphesenti elilinganiselwe lamacala.
2. Indlela yokuncibilikisa i-HPMC emanzini
2.1 Indlela yamanzi ashisayo
Njengoba i-hypromellose ingancibiliki emanzini ashisayo, ingasakazwa ngokulinganayo emanzini ashisayo esigabeni sokuqala, bese kuthi lapho isipholile, izindlela ezimbili ezijwayelekile zichazwe kanje:
(1) Faka inani elidingekayo lamanzi ashisayo esitsheni bese uwushisa ufike ku-70°C. Faka kancane kancane umkhiqizo ngaphansi kokuxubha kancane. Ekuqaleni, umkhiqizo untanta phezu kwamanzi, bese kancane kancane wakha i-slurry. Pholisa i-slurry.
(2) Faka i-1/3 noma i-2/3 yenani lamanzi elidingekayo esitsheni bese ulishisa ku-70°C ukuze usakaze umkhiqizo ukuze ulungiselele i-slurry yamanzi ashisayo, bese ufaka inani elisele lamanzi abandayo noma amanzi eqhwa ku-slurry yamanzi ashisayo. Ku-slurry, pholisa ingxube ngemva kokuyixuba.
2.2 Indlela yokuxuba ufulawa
Izinhlayiya zempuphu kanye nezinye izithako eziwumpuphu ezinenani elilinganayo noma elikhulu zihlakazwa ngokuphelele ngokuxuba okomile, bese kufakwa amanzi ukuze ancibilike. Ngalesi sikhathi, i-hypromellose ingancibilika ngaphandle kokuhlanganiswa.
3. Izinzuzo ze-HPMC
3.1 Ukuncibilika kwamanzi abandayo
Iyancibilika emanzini abandayo angaphansi kuka-40°C noma i-ethanol engu-70%. Ayincibiliki emanzini ashisayo angaphezu kuka-60°C, kodwa ingaxutshwa nejeli.
3.2 Ukungasebenzi kahle kwamakhemikhali
I-Hypromellose (HPMC) uhlobo lwe-non-ionic cellulose ether. Isixazululo sayo asinayo i-ionic charge futhi asihlangani nosawoti wensimbi noma ama-ionic organic compounds. Ngakho-ke, ezinye izinto ezisizayo azisabelani nayo ngesikhathi senqubo yokulungiselela.
3.3 Ukuqina
Izinzile kakhulu kokubili ku-acid kanye ne-alkali, futhi ingagcinwa isikhathi eside phakathi kwe-pH 3 kuya ku-1l, futhi i-viscosity yayo ayinalo ushintsho olucacile. Isixazululo samanzi se-hypromellose (HPMC) sinomphumela wokulwa nesikhunta futhi singagcina ukuqina okuhle kwe-viscosity ngesikhathi sokugcina isikhathi eside. Izinto ezisetshenziswa emithini ezisebenzisa i-HPMC zinokuqina okungcono kunezo ezisebenzisa izinto ezisetshenziswayo zendabuko (njenge-dextrin, isitashi, njll.).
3.4 Ukulungiswa kwe-viscosity
Izinhlobo ezahlukene ze-viscosity derivatives ze-HPMC zingaxutshwa ngezilinganiso ezahlukene, futhi i-viscosity yayo ingashintsha ngokuya ngomthetho othile, futhi inobuhlobo obuhle obuqondile, ngakho ingakhethwa ngokuya ngezidingo.
3.5 I-Metabolic inertia
I-HPMC ayimuncwa noma ayigaywa emzimbeni, futhi ayinikezi amakhalori, ngakho-ke iyisithako esiphephile semithi.
3.6 Ukuphepha
Ngokuvamile kukholelwa ukuthi i-HPMC ayiyona into enobuthi futhi ayicasuli. Umthamo ophakathi obulalayo wamagundane ungu-5g/kg, kanti umthamo ophakathi obulalayo wamagundane ungu-5.2g/kg. Umthamo wansuku zonke awunangozi emzimbeni womuntu.
4. Ukusetshenziswa kwe-HPMC kumalungiselelo
4.1 Isetshenziswa njengezinto zokumboza ifilimu kanye nezinto zokwakha ifilimu
I-Hypromellose (HPMC) isetshenziswa njengezinto zethebhulethi ezimbozwe ngefilimu. Uma kuqhathaniswa namaphilisi ambozwe ngefilimu endabuko njengamaphilisi ambozwe ngeshukela, amaphilisi ambozwe ngefilimu awanazo izinzuzo ezicacile zokufihla ukunambitheka nokubukeka, kodwa ubulukhuni bawo kanye nokugoba kwawo, ukumuncwa komswakama, ukubola, ukukhuluphala kwesisindo kanye nezinye izinkomba zekhwalithi kungcono. Izinga lokuqina eliphansi lalo mkhiqizo lisetshenziswa njengezinto zokugqoka ifilimu ezincibilika emanzini zamaphilisi namaphilisi, kanti izinga lokuqina okuphezulu lisetshenziswa njengezinto zokugqoka ifilimu zezinhlelo ze-organic solvent. Ukuhlushwa kokusetshenziswa ngokuvamile kungama-2.0%-20%.
4.2 njengesihlanganisi kanye nesihlukanisi
Izinga lokuqina eliphansi lalo mkhiqizo lingasetshenziswa njenge-binder kanye ne-disintegrant yamaphilisi, amaphilisi, kanye nama-granule, kanti izinga lokuqina okuphezulu lingasetshenziswa kuphela njenge-binder. Umthamo uyahlukahluka kuye ngamamodeli ahlukene kanye nezidingo. Ngokuvamile, inani le-binder elisetshenziselwa amaphilisi e-granulation eyomile lingu-5%, kanti inani le-binder elisetshenziselwa amaphilisi e-granulation emanzi lingu-2%.
4.3 Njenge-ejenti emisa okwesikhashana
I-ejenti yokumisa iyisithako sejeli esinobuthi futhi esinobuthi obungenamanzi. Ukusetshenziswa kwe-ejenti yokumisa ku-ejenti yokumisa kunganciphisa ijubane lokusaphaza kwezinhlayiya, futhi inganamatheliswa ebusweni bezinhlayiya ukuvimbela izinhlayiya ukuthi zingabi yi-polymer futhi zijiye zibe yinqwaba. Ama-ejenti okumisa adlala indima ebalulekile ekukhiqizweni kwama-suspension. I-HPMC iyinhlobo enhle kakhulu yama-ejenti okumisa. Isixazululo se-colloidal esincibilikisiwe kuyo singanciphisa ukucindezeleka kwe-interface ye-liquid-solid kanye namandla akhululekile ezinhlayiyeni ezincane eziqinile, ngaleyo ndlela kuthuthukiswe ukuzinza kohlelo lokusabalala olungafani. Lo mkhiqizo uwukulungiswa koketshezi lokumisa olunobuthi obuphezulu olulungiselelwe njenge-ejenti yokumisa. Unomphumela omuhle wokumisa, kulula ukuwuhlakaza kabusha, awunamatheli, futhi izinhlayiya ezincane ezigoqekile. Inani elivamile lingu-0.5% kuya ku-1.5%.
4.4 Isetshenziswa njengesivimbeli, i-ejenti yokukhulula ehamba kancane nelawulwayo kanye ne-ejenti yokwakha ama-pore
Izinga eliphezulu lokuthamba kwalo mkhiqizo lisetshenziselwa ukulungiselela amaphilisi e-hydrophilic gel matrix sustainable-release, ama-retarders kanye nama-controlled-release agents amaphilisi e-mixed-matrix sustainable-release. Linomphumela wokulibazisa ukukhishwa kwemithi. Ukuhlushwa kokusetshenziswa kwalo kungu-10% ~ 80% (W /W). Izinga eliphansi lokuthamba lisetshenziswa njenge-ejenti eyakha imbobo yezindlela zokukhululwa eziqhubekayo noma ezilawulwayo. Umthamo wokuqala odingekayo womphumela wokwelapha walolu hlobo lwethebhulethi ungafinyelelwa ngokushesha, bese kuba nomphumela wokukhululwa oqhubekayo noma olawulwayo, futhi ukuhlushwa kwemithi yegazi okusebenzayo kugcinwa emzimbeni. I-Hypromellose iyamanzisa ukuze yakhe ungqimba lwejeli lapho ihlangana namanzi. Indlela yokukhululwa kwemithi kusuka kuthebhulethi ye-matrix ikakhulukazi ukusabalala kongqimba lwejeli kanye nokuguguleka kongqimba lwejeli.
4.5 Iglue evikelayo esetshenziswa njengesithambisi kanye ne-colloid
Uma lo mkhiqizo usetshenziswa njengesithambisi, ukuhlushwa okuvamile kungu-0.45% ~ 1.0%. Lo mkhiqizo ungandisa futhi ukuzinza kweglue engangenisi amanzi, wakhe i-colloid evikelayo, uvimbele ukuhlangana kwezinhlayiya kanye nokuhlangana, ngaleyo ndlela uvimbele ukwakheka kwezinsalela. Ukuhlushwa kwawo okuvamile kungu-0.5% ~ 1.5%.
4.6 Kusetshenziswa njengento ye-capsule
Ngokuvamile, izinto zegobolondo le-capsule ze-capsule ziyi-gelatin ikakhulukazi. Inqubo yokukhiqiza igobolondo le-capsule le-Ming ilula, kodwa kunezinkinga ezithile kanye nezimo ezifana nokuvikelwa okungekuhle kwemithi ezwela umswakama kanye nomoya-mpilo, ukunciphisa ukuncibilika kwemithi, kanye nokubambezeleka kokuqhekeka kwegobolondo le-capsule ngesikhathi sokugcina. Ngakho-ke, i-hypromellose isetshenziswa esikhundleni sezinto ze-capsule ekulungiseleleni ama-capsule, okuthuthukisa ukubumba kanye nomphumela wokusetshenziswa kwe-capsule, futhi ikhuthazwe kabanzi ekhaya nakwamanye amazwe.
4.7 Njengesinamathelisi sezinto eziphilayo
Ubuchwepheshe bokunamathela kwe-bioadhesive, ukusetshenziswa kwezinto ezisizayo ngama-polymers anamathelayo, ngokunamathela ku-mucosa yezinto eziphilayo, kuthuthukisa ukuqhubeka nokuqina kokuxhumana phakathi kokulungiselela kanye ne-mucosa, ukuze umuthi ukhishwe kancane kancane futhi umuncwe yi-mucosa ukuze kufezwe inhloso yokwelashwa. Usetshenziswa kabanzi manje. Usetshenziselwa ukwelapha izifo zomgodi wamakhala kanye ne-mucosa yomlomo. Ubuchwepheshe bokunamathela kwe-bioadhesion yesisu uhlobo olusha lohlelo lokulethwa kwemithi oluthuthukiswe eminyakeni yamuva. Alwandisi nje kuphela isikhathi sokuhlala kwamalungiselelo emithi endleleni yokugaya ukudla, kodwa futhi luthuthukisa ukusebenza kokuthinta umuthi ne-membrane yeseli yendawo yokumunca futhi lushintsha ukugeleza kwe-membrane yeseli. Amandla okungena komuthi kumaseli e-epithelial amathumbu amancane ayathuthukiswa, ngaleyo ndlela kuthuthukiswe ukutholakala kwe-bioavailability komuthi.
4.8 Njengejeli yokugcoba
Njengomuthi wokunamathisela esikhumbeni, ijeli inezinzuzo eziningi ezifana nokuphepha, ubuhle, ukuhlanza okulula, izindleko eziphansi, inqubo elula yokulungiselela, kanye nokuhambisana kahle nemithi. Eminyakeni yamuva nje, ithole ukunakwa okukhulu futhi isibe ukuthuthukiswa kokulungiswa kwangaphandle kwesikhumba.
4.9 Njengesivimbeli semvula ohlelweni lwe-emulsification
Isikhathi sokuthunyelwe: Disemba 16-2021