1. Iimpawu ezisisiseko ze-HPMC
I-Hypromellose, igama elipheleleyo i-hydroxypropyl methylcellulose, i-alias HPMC. I-formula yayo ye-molecular C8H15O8-(C10Hl8O6)n-C8Hl5O8, kwaye ubunzima bayo be-molecular malunga ne-86000. Le mveliso yinto ye-semi-synthetic, eyingxenye ye-methyl kunye nenxalenye ye-polyhydroxypropyl ether ye-cellulose. Inokuveliswa ngeendlela ezimbini: enye kukuba ibakala elifanelekileyo le-methyl cellulose liphathwa nge-NaOH, kwaye liphendule ngepropylene oxide phantsi kobushushu obuphezulu kunye noxinzelelo. Ifom ixhunywe kwindandatho ye-anhydroglucose ye-cellulose, kwaye inokufikelela kwinqanaba elifanelekileyo; enye kukunyanga i-cotton linter okanye i-wood pulp fiber nge-caustic soda, kwaye uphendule nge-methyl chloride kunye ne-propylene oxide ngokulandelelana ukuyifumana, emva koko ucokise ngakumbi, utyunyuzwe ukwenza umgubo ococekileyo kunye nofanayo okanye iigranules. I-HPMC yintlobo ngeentlobo zeselulosi yezityalo zendalo, kwaye ikwayi-excipient egqwesileyo yamayeza, enoluhlu olubanzi lwemithombo. Okwangoku, isetyenziswa kakhulu ekhaya nakwamanye amazwe, kwaye yenye yezinto ezincedisa amayeza ezinezinga eliphezulu lokusetyenziswa kumachiza omlomo.
Le mveliso imhlophe ukuya kumhlophe obisi ngombala, ayinayo ityhefu kwaye ayinancasa, kwaye ikwimo yegranular okanye ifibrous powder ehamba lula. Izinzile phantsi kokukhanya kunye nokufuma. Ivuvukala emanzini abandayo ukwenza isisombululo esimhlophe se-milky colloidal, esinomlinganiselo othile we-viscosity, kwaye i-phenomenon ye-sol-gel interconversion ingenzeka ngenxa yokutshintsha kweqondo lokushisa loxinzelelo oluthile lwesisombululo. Inyibilika kakhulu kwi-70% yotywala okanye i-dimethyl ketone, kwaye ayiyi kunyibilika kwi-alcohol, i-chloroform okanye i-ethoxyethane.
Xa i-pH ye-hypromellose iphakathi kwe-4.0 kunye ne-8.0, inozinzo oluhle, kwaye ingaba khona ngokuzinzileyo xa i-pH iphakathi kwe-3.0 kunye ne-11.0. Xa iqondo lobushushu lingama-20°C kunye nokufuma okungama-80%, kugcinwa iintsuku ezili-10. I-coefficient yokufunxa ukufuma kwe-HPMC yi-6.2%.
Ngenxa yemixholo eyahlukeneyo ye-methoxy kunye ne-hydroxypropyl kwisakhiwo se-hypromellose, iintlobo ezahlukeneyo zeemveliso ziye zavela. Kwiindawo ezithile, iintlobo ezahlukeneyo zeemveliso zine-viscosity ethile kunye namaqondo okushisa e-Thermal gelation, ngoko ke, zineempawu ezahlukeneyo kwaye zingasetyenziselwa iinjongo ezahlukeneyo. I-pharmacopoeias zamazwe ahlukeneyo zinemimiselo eyahlukeneyo kunye nokubonakaliswa kwiimodeli: i-European Pharmacopoeia, ngokwemigangatho eyahlukeneyo ye-viscosities eyahlukeneyo kunye neqondo lokuthatha indawo yeemveliso ezithengiswa kwimarike, imelwe ngamabakala kunye namanani, kwaye iyunithi yi-mPa. ·s eUnited States Pharmacopoeia, igama eliqhelekileyo Yongeza amadijithi ama-4 ekupheleni ukubonisa umxholo kunye nodidi lwendawo nganye ye-hypromellose, efana ne-hypromellose 2208, amanani amabini okuqala amele ipesenti eqikelelweyo ye-methoxy, kwaye idijithi ezimbini zokugqibela zimele i-hydroxypropyl. Ipesenti eqikelelweyo.
2. Indlela yokunyibilikisa i-HPMC emanzini
2.1 indlela yamanzi ashushu
Ekubeni i-hypromellose ayinyibiliki emanzini ashushu, inokuchithwa ngokufanayo emanzini atshisayo ekuqaleni, kwaye ipholile. Iindlela ezimbini eziqhelekileyo zichazwa ngolu hlobo lulandelayo:
(1) Beka umlinganiselo ofunekayo wamanzi ashushu kwisikhongozeli, kwaye uyifudumeze ukuya kuma-70°C, ukongeza ngokuthe ngcembe le mveliso phantsi kokuvuselela okucothayo, ekuqaleni, le mveliso idada phezu kwamanzi, emva koko yenza ludaka, luxhokonxa Ukupholisa uludaka phantsi.
(2) Yongeza i-1/3 okanye i-2/3 yomthamo ofunekayo wamanzi kwisikhongozelo kwaye uyifudumeze ukuya kuma-70°C ukusasaza imveliso ukulungiselela udaka lwamanzi ashushu, uze wongeze umlinganiselo oseleyo wamanzi abandayo okanye amanzi omkhenkce de i-silts yamanzi ashushu Kwi-slurry, umxube upholile emva kokuvuselela.
2.2 Indlela yokuxuba umgubo
Iingqungquthela ze powder zichithwa ngokupheleleyo ngokuxuba okomileyo kunye nomlinganiselo olinganayo okanye omkhulu wezinye izithako ze powdery, kwaye zichithwa emanzini. Ngeli xesha, i-hypromellose inokuchithwa ngaphandle kwe-agglomeration.
3. Izinto eziluncedo zeHPMC
3.1 Ukunyibilika kwamanzi abandayo
Inyibilika kumanzi abandayo angaphantsi kwe-40 ° C okanye i-70% ye-ethanol, ngokusisiseko ayinyibiliki emanzini ashushu angaphezu kwama-60 ° C, kodwa inokuthi ifakwe i-gel.
3.2 Ukungangeni ngamachiza
IHypromellose (HPMC) luhlobo lwe-ether ye-cellulose engeyiyo ionic. Isisombululo sayo asinayo i-ionic kwaye ayisebenzisi kunye neetyuwa zetsimbi okanye i-ionic organic compounds. Ngoko ke, abanye abancedisi abaphenduli kunye nayo ngexesha lenkqubo yokulungiselela.
3.3 Uzinzo
Izinzile kwi-asidi kunye ne-alkali, kwaye inokugcinwa ixesha elide phakathi kwe-pH 3 kunye ne-1l ngaphandle kotshintsho olucacileyo kwi-viscosity. Isisombululo se-aqueous se-hypromellose (HPMC) sinefuthe elichasayo kwaye sinokugcina uzinzo oluhle lwe-viscosity ngexesha lokugcinwa kwexesha elide. Amachiza asebenzisa i-HPMC njengabancedisi banozinzo olungcono lomgangatho kunezo zisebenzisa izincedisi zesintu (ezifana ne-dextrin, istatshi, njl.).
3.4 Ukulungelelaniswa kweViscosity
I-viscosity derivatives eyahlukeneyo ye-HPMC inokuxutywa ngokwemilinganiselo eyahlukeneyo, kwaye i-viscosity yayo inokutshintsha ngokwemigaqo ethile, kwaye inobudlelwane obuhle bomgca, ngoko umlinganiselo unokukhethwa ngokweemfuno.
3.5 Inertia yeMetabolic
I-HPMC ayifunxanga okanye ixutywe emzimbeni, kwaye ayiboneleli ngobushushu, ngoko ke iyindawo ekhuselekileyo yokulungiselela amayeza.
3.6 Ukhuseleko
Kukholelwa ngokubanzi ukuba i-HPMC yinto engeyotyhefu kwaye ayithukuthezi. Idosi ebulalayo ephakathi kwiigundane yi-5g / kg, kwaye i-dose ebulalayo ephakathi kwiigundane yi-5.2g / kg. Iidosi zemihla ngemihla azinabungozi ebantwini.
4. Ukusetyenziswa kweHPMC kumalungiselelo
4.1 Njengezinto zokugquma ifilimu kunye nezixhobo zokwenza ifilimu
Ukusebenzisa i-hypromellose (HPMC) njengesixhobo sethebhulethi efakwe ifilimu, xa kuthelekiswa neetafile ezigqunywe ngokwesiko ezifana neetafile ezigqunywe ngeswekile, iitafile ezigqunywe ngeswekile azinanzuzo zicacileyo zokufihla incasa yeyeza kunye nenkangeleko, kodwa ukuqina kunye nokuqina, ukufunxa ukufuma, ukuqhekeka, ukuzuza ubunzima bokugquma kunye nezinye izikhombisi zekhwalithi zingcono. Ibanga eliphantsi le-viscosity yale mveliso lisetyenziswa njengento yokugubungela ifilimu ene-soluble yamanzi kwiipilisi kunye neepilisi, kwaye ibakala eliphezulu le-viscosity lisetyenziswa njengento yokugubungela ifilimu kwiinkqubo ze-solvent ze-organic. Ukugxininiswa ngokuqhelekileyo yi-2.0% ukuya kwi-20%.
4.2 Njengomdibanisi kunye ne-disintegrant
Ibakala eliphantsi le-viscosity yale mveliso lingasetyenziselwa njenge-binder kunye ne-disintegrant yamacwecwe, iipilisi, kunye ne-granules, kwaye i-high-viscosity grade ingasetyenziswa kuphela njenge-binder. Idosi iyahluka ngeemodeli ezahlukeneyo kunye neemfuno. Ngokuqhelekileyo, idosi ye-binder kwiipilisi ezomileyo ze-granulation yi-5%, kunye ne-dosage ye-binder kwiipilisi ezimanzi ze-granulation yi-2%.
4.3 Njenge-arhente exhomayo
I-agent yokumisa i-viscous gel substance ene-hydrophilicity, enokunciphisa isantya se-sedimentation yamasuntswana xa isetyenziswe kwi-arhente yokumisa, kwaye inokudityaniswa kumphezulu weengqungquthela ukukhusela amaqhekeza ukuba adibanise kunye nokuncipha kwibhola. . Iiarhente ezixhomayo zidlala indima ebalulekileyo ekwenzeni ukunqunyanyiswa. I-HPMC luhlobo olugqwesileyo lweearhente zokuxhoma, kunye nesisombululo sayo esinyibilikisiweyo se-colloidal sinokunciphisa ukuxinana kojongano olululwelo oluqinileyo kunye namandla asimahla kumasuntswana amancinane aqinileyo, ngaloo ndlela aphucula uzinzo lwenkqubo yokusasazwa kwe-heterogeneous. Ibakala eliphezulu le-viscosity yale mveliso lisetyenziselwa ukulungiswa kolwelo olumisiweyo olulungiselelwe njenge-arhente yokumisa. Inesiphumo esihle sokuxhoma, kulula ukuphinda isasazeke, ayibambeleli eludongeni, kwaye inamasuntswana athambileyo. Idosi eqhelekileyo yi-0.5% ukuya kwi-1.5%.
4.4 Njenge-blocker, i-arhente yokukhululwa okuqhubekayo kunye ne-arhente ebangela i-pore-causing
Ibanga eliphezulu le-viscosity yale mveliso lisetyenziselwa ukulungiselela i-hydrophilic gel matrix yokukhululwa okuqhubekayo, i-blockers kunye ne-controlled-release agents kwi-mixed material matrix ukukhululwa okuqhubekayo kweepilisi, kwaye inefuthe lokulibazisa ukukhutshwa kweziyobisi. Ukugxininiswa kokusetyenziswa kwayo yi-10% ~ 80% (W / W). Amanqanaba e-low-viscosity asetyenziswa njenge-pore-forming agents ukwenzela ukukhululwa okuqhubekayo okanye ukukhutshwa okulawulwayo kwamalungiselelo. Idosi yokuqala efunekayo kwisiphumo sonyango solu hlobo lwethebhulethi inokufezekiswa ngokukhawuleza, kwaye emva koko ikhuphe isiphumo esizinzileyo okanye esilawulwayo sokukhululwa, kwaye ukugxininiswa kweziyobisi okusebenzayo kugcinwa emzimbeni. Xa i-hypromellose idibana namanzi, igalela amanzi ukuze yenze umaleko wejeli. Indlela yokukhutshwa kweziyobisi kwithebhulethi ye-matrix ikakhulu ibandakanya ukusasazwa komgangatho wejeli kunye nokukhukuliseka komgangatho wejeli.
4.5 Iglu ekhuselayo njenge-thickener kunye ne-colloid
Xa le mveliso isetyenziswa njenge-thickener, i-concentration esetyenziswa ngokuqhelekileyo yi-0.45% ~ 1.0%. Le mveliso inokunyusa ukuzinza kweglue ye-hydrophobic, yenza i-colloid ekhuselayo, ithintele amaqhekeza kwi-agglomerating kunye ne-agglomerating, ngaloo ndlela inqanda ukubunjwa kwentlenga, kunye nokugxininiswa kwayo ngokuqhelekileyo yi-0.5% ~ 1.5%.
4.6 Izinto ze-Capsule kwii-capsules
Ngokuqhelekileyo i-capsule shell capsule impahla ye-capsule isekelwe kwi-gelatin. Inkqubo yokuveliswa kwegobolondo ye-gelatin capsule ilula, kodwa kukho ezinye iingxaki kunye neziganeko ezifana nokukhuselwa kakubi kumanzi kunye ne-oxygen iziyobisi ezibuthathaka, izinga eliphantsi lokuchithwa kweziyobisi, kunye nokulibaziseka ukuchithwa kwegobolondo le-capsule ngexesha lokugcinwa. Ngoko ke, i-hypromellose, njenge-substitute ye-gelatin capsules, isetyenziselwa ukulungiswa kwee-capsules, eziphucula ukubunjwa kunye nokusetyenziswa kwefuthe le-capsules, kwaye iye yakhuthazwa ngokubanzi ekhaya nakwamanye amazwe.
4.7 njenge-bioadhesive
Itekhnoloji ye-Bioadhesion, ukusetyenziswa kwe-excipients kunye ne-polymers ye-bioadhesive, ngokunamathela kwi-mucosa ye-biological, iphakamisa ukuqhubeka kunye nokuqina koqhagamshelwano phakathi kokulungiswa kunye ne-mucosa, ukuze ichiza likhutshwe ngokukhawuleza kwaye lifunxwe yi-mucosa ukufezekisa iinjongo zonyango. Okwangoku isetyenziswa ngokubanzi Isetyenziselwa ukunyanga izifo ze-nasal cavity, i-mucosa yomlomo kunye nezinye iindawo. Itekhnoloji ye-bioadhesion ye-gastrointestinal yinkqubo entsha yokuhanjiswa kwechiza ephuhliswe kwiminyaka yakutshanje. Ayinakwandisa nje ixesha lokuhlala lamalungiselelo amayeza kwindlela yesisu, kodwa ikwaphucula ukusebenza koqhagamshelwano phakathi kwechiza kunye nenwebu yeseli kwindawo yokufunxa, ukuguqula ulwelo lwenwebu yeseli, Ukuphucula ukungena kwechiza emathunjini. iiseli epithelial, ngaloo ndlela kuphuculwe bioavailability ichiza.
4.8 Njengejeli yezihloko
Njengokulungiselela ukunamathela kwesikhumba, i-gel inoluhlu lweenzuzo ezifana nokhuseleko, ubuhle, ukucocwa lula, ixabiso eliphantsi, inkqubo yokulungiselela elula, kunye nokuhambelana kakuhle neziyobisi. ulwalathiso.
Ixesha lokuposa: Dec-15-2022