1. Uhlobo olusisiseko lwe-HPMC
IHypromellose, igama lesiNgesi elithi hydroxypropyl methylcellulose, elibizwa ngokuba yiHPMC. Ifomula yayo yemolekyuli yiC8H15O8-(C10Hl8O6)n-C8Hl5O8, kwaye ubunzima bemolekyuli bumalunga nama-86,000. Le mveliso yinto eyenziwe ngokwe-semi-synthetic, eyinxalenye yeqela le-methyl kunye nenxalenye ye-polyhydroxypropyl ether ye-cellulose. Ingenziwa ngeendlela ezimbini: enye kukuphatha i-methyl cellulose yodidi olufanelekileyo nge-NaOH, ize emva koko iphendule nge-propylene oxide phantsi kobushushu obuphezulu kunye noxinzelelo oluphezulu. Ixesha lokuphendula kufuneka ligcinwe ukuvumela amaqela e-methyl kunye ne-hydroxypropyl ukuba adibane ne-ether. Uhlobo lwe- luqhagamshelwe kwindandatho ye-anhydroglucose ye-cellulose, kwaye inokufikelela kwinqanaba elifunekayo; enye kukuphatha i-cotton linter okanye i-wood pulp fiber nge-caustic soda, ize emva koko ifumaneke ngokuphendula nge-chlorinated methane kunye ne-propylene oxide ngokulandelelana, ize emva koko ihlanjululwe ngakumbi, i-Pulverize, yenze ibe ngumgubo okanye i-granule ecolekileyo nefanayo. I-HPMC luhlobo lwe-cellulose yezityalo zendalo, kwaye ikwangumxumi obalaseleyo wamayeza, onomthombo obanzi. Okwangoku, isetyenziswa kakhulu ekhaya nakwamanye amazwe, kwaye yenye yezona zinto zisetyenziswa kakhulu ngamayeza asetyenziswa ngomlomo.
Umbala wale mveliso umhlophe ukuya kumhlophe ofana nobisi, awunatyhefu kwaye awunancasa, kwaye yimpuphu ethambileyo okanye enemicu, ehamba lula. Izinzile xa ikhanyiswe ngokukhanya kunye nokufuma. Idumba emanzini abandayo ukuze yenze isisombululo se-colloidal esimhlophe esifana nobisi esinezinga elithile le-viscosity. Imeko yokuguqulwa kwe-sol-gel inokwenzeka ngenxa yokutshintsha kobushushu boxinzelelo oluthile lwesisombululo. Kulula kakhulu ukunyibilikisa kwi-70% yotywala okanye i-dimethyl ketone, kwaye ayizukunyibilikisa kwi-anhydrous alcohol, i-chloroform okanye i-ethoxyethane.
IHypromellose izinzile kakuhle xa i-pH iphakathi kwe-4.0 kunye ne-8.0, kwaye inokuhlala izinzile phakathi kwe-3.0 kunye ne-11.0. Emva kokugcinwa iintsuku ezili-10 kubushushu obungama-20°C kunye nokufuma okulinganiselweyo kwe-80%, i-HPMC ifunxa umswakama yi-6.2%.
Ngenxa yomahluko kumxholo wezinto ezimbini ezithatha indawo kwisakhiwo se-hypromellose, i-methoxy kunye ne-hydroxypropyl, kuye kwavela iintlobo ezahlukeneyo zeemveliso. Kwi-concentration ethile, iintlobo ezahlukeneyo zeemveliso zine-viscosity ethile kwaye ubushushu be-Thermal gelation, ngoko ke, buneempawu ezahlukeneyo kwaye bunokusetyenziswa ngeenjongo ezahlukeneyo. Ii-pharmacopoeia zamazwe ahlukeneyo zineenkcukacha ezahlukeneyo kunye neenkcazo zemodeli: I-European Pharmacopoeia isekelwe kwiindidi ezahlukeneyo ze-viscosities ezahlukeneyo kunye namanqanaba ahlukeneyo okutshintshwa kweemveliso ezikwimarike. Ibonakaliswa yi-grade kunye nenani. Iyunithi yi-mPa•s. Emva kokongeza amanani ama-4 ukubonisa umxholo kunye nohlobo lwe-substituent nganye ye-hypromellose, umzekelo, i-hypromellose 2208, amanani amabini okuqala amele ipesenti eqikelelweyo yeqela le-methoxy, amanani amabini okugqibela amele i-hydroxypropyl Ipesenti eqikelelweyo yamatyala.
2. Indlela yokunyibilikisa i-HPMC emanzini
2.1 Indlela yamanzi ashushu
Ekubeni i-hypromellose inganyibiliki emanzini ashushu, inokusasazeka ngokulinganayo emanzini ashushu kwinqanaba lokuqala, kwaye xa ipholile, iindlela ezimbini eziqhelekileyo zichazwa ngolu hlobo lulandelayo:
(1) Faka umlinganiselo ofunekayo wamanzi ashushu kwisitya uze uwufudumeze ukuya kuthi ga kwi-70℃. Yongeza kancinci kancinci imveliso xa uyixuba kancinci. Ekuqaleni, imveliso iyadada phezu kwamanzi, ize emva koko yenze i-slurry kancinci kancinci. Pholisa i-slurry.
(2) Yongeza i-1/3 okanye i-2/3 yamanzi afunekayo kwisikhongozeli uze uyifudumeze ukuya kuma-70°C ukuze usasaze imveliso ukulungiselela i-slurry yamanzi ashushu, uze wongeze amanzi abandayo okanye amanzi omkhenkce aseleyo kwi-slurry yamanzi ashushu. Kwi-slurry, pholisa umxube emva kokuwuxuba.
2.2 Indlela yokuxuba umgubo
Amasuntswana omgubo kunye nezinye izithako ezinjengomgubo ezilinganayo okanye ezinkulu zisasazwa ngokupheleleyo ngokuxuba okomileyo, emva koko kongezwa amanzi ukuze anyibilike. Ngeli xesha, i-hypromellose inokunyibilika ngaphandle kokuhlanganiswa.
3. Iingenelo ze-HPMC
3.1 Ukunyibilika kwamanzi abandayo
Iyanyibilika emanzini abandayo angaphantsi kwama-40°C okanye i-ethanol engama-70%. Ayinyibiliki emanzini ashushu angaphezu kwama-60°C, kodwa inokunyibilika.
3.2 Ukungangeni kakuhle kweekhemikhali
IHypromellose (HPMC) luhlobo lwe-non-ionic cellulose ether. Isisombululo sayo asinayo i-ionic charge kwaye asidibani neetyuwa zesinyithi okanye ii-ionic organic compounds. Ke ngoko, ezinye izinto ezincedisayo azisabelani nayo ngexesha lenkqubo yokulungiselela.
3.3 Uzinzo
Izinzile kwi-asidi kunye ne-alkali, kwaye ingagcinwa ixesha elide phakathi kwe-pH 3 ukuya kwi-1l, kwaye i-viscosity yayo ayinatshintsho lucacileyo. Isisombululo samanzi se-hypromellose (HPMC) sinefuthe lokulwa nokungunda kwaye sinokugcina uzinzo oluhle lwe-viscosity ngexesha lokugcina ixesha elide. Izinto ezisetyenziswa ngamayeza ezisebenzisa i-HPMC zinozinzo olungcono kunolo zisebenzisa izinto ezisetyenziswa ngamayeza zemveli (ezifana ne-dextrin, istarch, njl.njl.).
3.4 Ukulungiswa kwe-viscosity
Ii-viscosity derivatives ezahlukeneyo ze-HPMC zinokuxutywa ngobuninzi obahlukeneyo, kwaye i-viscosity yayo inokutshintsha ngokomthetho othile, kwaye inobudlelwane obuhle obuthe ngqo, ngoko ke inokukhethwa ngokweemfuno.
3.5 I-Metabolic inertia
I-HPMC ayifunxwa okanye ayigaywanga emzimbeni, kwaye ayiboneleli ngeekhalori, ngoko ke ingumphelelisi okhuselekileyo kwimveliso yamayeza.
3.6 Ukhuseleko
Ngokwesiqhelo kukholelwa ukuba i-HPMC yinto engenabungozi kwaye ayibangeli buhlungu. Umlinganiselo ophakathi wokubulala iimpuku yi-5g/kg, kwaye umlinganiselo ophakathi wokubulala iimpuku yi-5.2g/kg. Umlinganiselo wemihla ngemihla awunabungozi emzimbeni womntu.
4. Ukusetyenziswa kwe-HPMC kumalungiselelo
4.1 Isetyenziswa njengezinto zokugquma ifilimu kunye nezinto zokwenza ifilimu
IHypromellose (HPMC) isetyenziswa njengesixhobo sethebhulethi esigqunywe ngefilimu. Xa kuthelekiswa neethebhulethi zemveli ezigqunywe ngeswekile, iithebhulethi ezigqunywe ngeswekile azinazo iingenelo ezicacileyo zokufihla incasa kunye nenkangeleko, kodwa ubulukhuni bazo kunye nokugungqa kwazo, ukufunxwa komswakama, ukuqhekeka, ukutyeba kunye nezinye izalathisi zomgangatho zingcono. Umgangatho we-viscosity ephantsi wale mveliso usetyenziswa njengesixhobo se-film coating esinyibilikayo emanzini kwiithebhulethi kunye neepilisi, kwaye umgangatho we-viscosity ephezulu usetyenziswa njengesixhobo se-film coating kwiinkqubo ze-organic solvent. Uxinzelelo lokusetyenziswa ludla ngokuba yi-2.0%-20%.
4.2 njengento edibanisayo nengasasebenziyo
Umgangatho we-viscosity ephantsi wale mveliso ungasetyenziswa njenge-binder kunye ne-disintegrant kwiipilisi, iipilisi, kunye nee-granules, kwaye umgangatho we-viscosity ephezulu ungasetyenziswa kuphela njenge-binder. Umthamo uyahluka ngokweemodeli kunye neemfuno ezahlukeneyo. Ngokubanzi, ubungakanani be-binder esetyenziselwa iipilisi ze-granulation ezomileyo yi-5%, kwaye ubungakanani be-binder esetyenziselwa iipilisi ze-granulation ezimanzi yi-2%.
4.3 Njengearhente enqumamisayo
I-agent yokuxhoma yinto yejeli ebhityileyo ene-hydrophilicity. Ukusetyenziswa kwe-agent yokuxhoma kwi-agent yokuxhoma kunokucothisa isantya sokutyibilika kwamasuntswana, kwaye inokuncamathiselwa kumphezulu wamasuntswana ukuthintela amasuntswana ekubeni apolime kwaye ajike abe yingqokelela. Ii-agent zokuxhoma zidlala indima ebalulekileyo ekuvelisweni kwamasuntswana. I-HPMC ludidi oluhle kakhulu lwee-agent zokuxhoma. Isisombululo se-colloidal esinyibilikiswe kuyo sinokunciphisa uxinzelelo lwe-interface yolwelo-oluqinileyo kunye namandla akhululekileyo kumasuntswana amancinci aqinileyo, ngaloo ndlela kuphucula uzinzo lwenkqubo yokusasazwa okuhlukeneyo. Le mveliso lulungiselelo lolwelo lokuxhoma oluphezulu olulungiselelwe njenge-agent yokuxhoma. Inesiphumo esihle sokuxhoma, kulula ukuyiphinda isasazeke, ayinamatheli, kwaye incinci i-flocculated particles. Ubungakanani obuqhelekileyo yi-0.5% ukuya kwi-1.5%.
4.4 Isetyenziswa njenge-blocker, i-arhente yokukhulula ecothayo nelawulwayo kunye ne-arhente yokwenza iimbobo
Umgangatho ophezulu we-viscosity wale mveliso usetyenziselwa ukulungiselela iipilisi ze-hydrophilic gel matrix sustainable-release, ii-retarders kunye nee-controlled-release agents zeepilisi ze-mixed-matrix sustainable-release. Inefuthe lokulibazisa ukukhululwa kwamayeza. Uxinzelelo lokusetyenziswa kwayo yi-10% ~ 80% (W /W). Umgangatho ophantsi we-viscosity usetyenziswa njenge-arhente yokwenza ii-pore kwiifomyula zokukhululwa eziqhubekayo okanye ezilawulwayo. Umthamo wokuqala ofunekayo kwisiphumo sonyango sale hlobo lwethebhulethi unokufikelelwa ngokukhawuleza, kwaye emva koko umphumo wokukhululwa oqhubekayo okanye olawulwayo uyasetyenziswa, kwaye uxinzelelo olusebenzayo lweziyobisi zegazi lugcinwa emzimbeni. I-Hypromellose i-hydrate ukwenza umaleko wejeli xa idibana namanzi. Indlela yokukhululwa kwamayeza kwithebhulethi ye-matrix ngokuyintloko kukusasazwa komaleko wejeli kunye nokukhukuliseka komaleko wejeli.
4.5 Iglu yokukhusela esetyenziswa njengesithambisi kunye ne-colloid
Xa le mveliso isetyenziswa njengesithambisi-manzi, uxinaniso oluqhelekileyo yi-0.45% ~ 1.0%. Le mveliso inokunyusa uzinzo lweglue enganyangekiyo emanzini, yenze i-colloid ekhuselayo, ithintele ukuhlangana kwamasuntswana kunye nokuhlangana, ngaloo ndlela ithintele ukwakheka kwenkunkuma. Uxinaniso lwayo oluqhelekileyo yi-0.5% ~ 1.5%.
4.6 Isetyenziswa njengesixhobo sekhaphu
Ngokwesiqhelo, izinto zegobolondo lekhaphukhaphu zekhaphu ikakhulu yigelatin. Inkqubo yokuvelisa igobolondo lekhaphukhaphu leMing ilula, kodwa kukho iingxaki kunye neziganeko ezithile ezifana nokukhuselwa okungalunganga kwamayeza abuthathaka kumswakama kunye neoksijini, ukunciphisa ukunyibilika kwamayeza, kunye nokulibaziseka kokuqhekeka kwegobolondo lekhaphukhaphu ngexesha lokugcinwa. Ke ngoko, i-hypromellose isetyenziswa endaweni yezinto zekhaphukhaphu xa kulungiswa iikhaphukhaphu, nto leyo ephucula ukubumbeka kunye nefuthe lokusetyenziswa kwekhaphukhaphu, kwaye ikhuthazwe kakhulu ekhaya nakwamanye amazwe.
4.7 Njengento yokuncamathelisa izinto eziphilayo
Itekhnoloji yokuncamathelisa i-bioadhesive, ukusetyenziswa kwezinto ezincedisayo kunye neepolymers ze-bioadhesive, ngokunamathela kwi-mucosa yebhayoloji, kuphucula ukuqhubeka kunye nokuqina koqhagamshelwano phakathi kolungiselelo kunye ne-mucosa, ukuze iyeza likhutshwe kancinci kwaye lifunxwe yi-mucosa ukufezekisa injongo yonyango. Isetyenziswa kakhulu ngoku Isetyenziselwa ukunyanga izifo zomngxuma wempumlo kunye ne-mucosa yomlomo. Itekhnoloji yokuncamathelisa i-bioadhesion yesisu luhlobo olutsha lwenkqubo yokuhambisa amayeza oluphuhliswe kwiminyaka yakutshanje. Ayigcini nje ngokwandisa ixesha lokuhlala kwamalungiselelo eziyobisi kwindlela yesisu, kodwa ikwaphucula ukusebenza koqhagamshelwano lweyeza kunye ne-membrane yeseli yendawo yokufunxa kwaye itshintsha ukugeleza kwe-membrane yeseli. Amandla okungena kwesi sidakamizwa kwiiseli ze-epithelial zamathumbu amancinci ayandiswa, ngaloo ndlela iphucula ukufumaneka kwesi sidakamizwa.
4.8 Njengejeli yokuthambisa
Njengelungiselelo lokuncamathelisa ulusu, ijeli ineenzuzo ezininzi ezifana nokhuseleko, ubuhle, ukucocwa okulula, iindleko eziphantsi, inkqubo yokulungiselela elula, kunye nokuhambelana okuhle namayeza. Kwiminyaka yakutshanje, ifumene ingqwalasela enkulu kwaye iye yaba luphuhliso lwendlela yokulungiselela ulusu lwangaphandle.
4.9 Njengesithinteli semvula kwinkqubo ye-emulsification
Ixesha lokuthumela: Disemba-16-2021