1. Qhov tseem ceeb ntawm HPMC
Hypromellose, lus Askiv lub npe hydroxypropyl methylcellulose, alias HPMC. Nws cov mis molecular yog C8H15O8-(C10Hl8O6)n-C8Hl5O8, thiab qhov hnyav molecular yog txog 86,000. Cov khoom no yog cov khoom siv hluavtaws, uas yog ib feem ntawm pawg methyl thiab ib feem ntawm polyhydroxypropyl ether ntawm cellulose. Nws tuaj yeem tsim los ntawm ob txoj hauv kev: ib qho yog kho cov methyl cellulose ntawm qib haum nrog NaOH, thiab tom qab ntawd ua rau cov propylene oxide nyob rau hauv qhov kub thiab txias. Lub sijhawm tshuaj tiv thaiv yuav tsum tau txhawb nqa kom cov methyl thiab hydroxypropyl pawg sib txuas nrog ether. Daim ntawv ntawm yog txuas nrog lub nplhaib anhydroglucose ntawm cellulose, thiab tuaj yeem ncav cuag qhov xav tau qib; lwm yam yog kho cov paj rwb linter los yog ntoo pulp fiber nrog caustic soda, thiab tom qab ntawd tau los ntawm reacting nrog chlorinated methane thiab propylene oxide successively, thiab tom qab ntawd ntxiv refined, Pulverize, ua rau zoo thiab uniform hmoov los yog granule. HPMC yog ntau yam ntawm cov nroj tsuag ntuj cellulose, thiab nws kuj yog ib qho zoo heev tshuaj excipient, uas muaj ib tug dav qhov chaw. Tam sim no, nws yog dav siv nyob rau hauv tsev thiab txawv teb chaws, thiab nws yog ib tug ntawm cov kws tshuaj excipients nrog lub siab tshaj plaws kev siv ntawm cov tshuaj qhov ncauj.
Cov xim ntawm cov khoom no yog dawb mus rau milky dawb, tsis muaj tshuaj lom thiab tsis qab, thiab nws yog ib qho granular lossis fibrous, yooj yim-ntws hmoov. Nws yog ib qho ruaj khov nyob rau hauv lub teeb raug thiab av noo. Nws swells nyob rau hauv dej txias los tsim ib tug milky dawb colloidal tov nrog ib tug tej yam degree ntawm viscosity. Lub sol-gel interconversion tshwm sim tuaj yeem tshwm sim vim qhov kub hloov pauv ntawm qee qhov kev daws teeb meem. Nws yooj yim heev rau yaj hauv 70% cawv lossis dimethyl ketone, thiab yuav tsis yaj hauv dej cawv, chloroform lossis ethoxyethane.
Hypromellose muaj kev ruaj ntseg zoo thaum pH nyob nruab nrab ntawm 4.0 thiab 8.0, thiab nws tuaj yeem nyob ruaj khov ntawm 3.0 thiab 11.0. Tom qab khaws cia rau 10 hnub ntawm qhov kub ntawm 20 ° C thiab qhov txheeb ze av noo ntawm 80%, Cov dej noo nqus coefficient ntawm HPMC yog 6.2%.
Vim tias qhov sib txawv ntawm cov ntsiab lus ntawm ob qhov hloov pauv hauv cov qauv ntawm hypromellose, methoxy thiab hydroxypropyl, ntau yam khoom tau tshwm sim. Nyob rau hauv ib qho tshwj xeeb concentration, ntau hom khoom muaj cov viscosity tshwj xeeb thiab Thermal gelation kub, yog li ntawd, muaj cov khoom sib txawv thiab tuaj yeem siv rau ntau lub hom phiaj. Lub pharmacopoeias ntawm ntau lub teb chaws muaj ntau yam kev qhia tshwj xeeb thiab kev qhia rau cov qauv: Cov European Pharmacopoeia yog nyob ntawm ntau qib ntawm cov viscosities sib txawv thiab qib sib txawv ntawm kev hloov pauv ntawm cov khoom hauv khw. Nws qhia los ntawm qib ntxiv rau tus lej. Chav tsev yog mPa•s. Tom qab ntxiv 4 tus lej los qhia txog cov ntsiab lus thiab hom ntawm txhua qhov hloov pauv ntawm hypromellose, piv txwv li, hypromellose 2208, thawj ob tus lej sawv cev rau kwv yees li feem pua ntawm methoxy pawg, ob tus lej kawg sawv cev rau hydroxypropyl kwv yees feem pua ntawm cov neeg mob.
2.Cov txheej txheem ntawm kev ua kom HPMC yaj hauv dej
2.1 Cov txheej txheem dej kub
Txij li thaum hypromellose tsis yaj hauv dej kub, nws tuaj yeem sib cais hauv dej kub thaum pib, thiab tom qab ntawd thaum nws txias, ob txoj hauv kev tau piav qhia raws li hauv qab no:
(1) Muab cov dej kub uas xav tau rau hauv lub thawv thiab ua kom sov li 70 ℃. Maj mam ntxiv cov khoom nyob rau hauv qeeb stirring. Thaum pib, cov khoom ntab saum npoo av, thiab tom qab ntawd maj mam tsim cov slurry. Txias lub slurry.
(2) Ntxiv 1/3 los yog 2/3 ntawm cov dej xav tau rau hauv lub thawv thiab kub rau 70 ° C kom tawg cov khoom los npaj cov dej kub slurry, thiab tom qab ntawd ntxiv cov dej txias lossis dej khov ntxiv. mus rau dej kub slurry Nyob rau hauv lub slurry, txias qhov sib tov tom qab stirring.
2.2 Txoj kev sib tov hmoov
Cov hmoov nplej thiab lwm cov khoom xyaw hmoov sib npaug lossis ntau dua yog tawg tag nrho los ntawm kev sib xyaw qhuav, thiab tom qab ntawd dej ntxiv rau yaj. Lub sijhawm no, hypromellose tuaj yeem yaj yam tsis muaj agglomeration.
3. Qhov zoo ntawm HPMC
3.1 Cov dej txias solubility
Nws yog soluble hauv dej txias hauv qab 40 ° C lossis 70% ethanol. Nws yog qhov yooj yim insoluble hauv dej kub siab tshaj 60 ° C, tab sis nws tuaj yeem gelled.
3.2 Chemical inertness
Hypromellose (HPMC) yog ib hom non-ionic cellulose ether. Nws cov tshuaj tsis muaj ionic nqi thiab tsis cuam tshuam nrog hlau ntsev los yog ionic organic tebchaw. Yog li ntawd, lwm cov excipients tsis hnov mob nrog nws thaum lub sijhawm npaj.
3.3 Kev ruaj ntseg
Nws yog qhov ruaj khov rau ob qho tib si acid thiab alkali, thiab tuaj yeem khaws cia rau lub sijhawm ntev ntawm pH 3 txog 1l, thiab nws cov viscosity tsis muaj qhov hloov pauv. Cov tshuaj aqueous ntawm hypromellose (HPMC) muaj cov nyhuv los tiv thaiv pwm thiab tuaj yeem tswj tau qhov zoo viscosity stability thaum lub sij hawm ntev cia. Cov tshuaj excipients uas siv HPMC muaj kev ruaj ntseg zoo dua li cov uas siv cov tshuaj excipients (xws li dextrin, starch, thiab lwm yam).
3.4 Adjustability ntawm viscosity
Qhov sib txawv viscosity derivatives ntawm HPMC tuaj yeem sib xyaw ua ke sib txawv, thiab nws cov viscosity tuaj yeem hloov pauv raws li txoj cai, thiab muaj kev sib raug zoo linear, yog li nws tuaj yeem xaiv raws li qhov yuav tsum tau ua.
3.5 Metabolic inertia
HPMC tsis absorbed los yog metabolized hauv lub cev, thiab tsis muab calories, yog li nws yog ib qho kev nyab xeeb excipient rau kev npaj tshuaj.
3.6 Kev ruaj ntseg
Nws feem ntau ntseeg tias HPMC yog cov khoom tsis muaj tshuaj lom thiab tsis ua rau khaus. Qhov nruab nrab koob tshuaj tuag rau nas yog 5g / kg, thiab qhov nruab nrab ntawm cov nas tua nas yog 5.2g / kg. Kev noj tshuaj txhua hnub tsis muaj teeb meem rau tib neeg lub cev.
4. Kev siv HPMC hauv kev npaj
4.1 Siv ua zaj duab xis txheej khoom thiab zaj duab xis tsim khoom
Hypromellose (HPMC) yog siv los ua cov khoom siv hauv cov ntsiav tshuaj. Piv nrog rau cov ntsiav tshuaj coated xws li qab zib-coated ntsiav tshuaj, cov ntsiav tshuaj coated tsis muaj qhov zoo tshaj plaws hauv kev npog qhov saj thiab tsos, tab sis lawv hardness thiab friability, noo noo nqus, disintegration, txheej hnyav nce thiab lwm yam kev ntsuas zoo dua. Cov qib qis viscosity ntawm cov khoom no yog siv los ua cov dej-soluble zaj duab xis txheej cov khoom siv rau cov ntsiav tshuaj thiab cov tshuaj, thiab qib high-viscosity yog siv los ua cov txheej txheem zaj duab xis rau cov kuab tshuaj organic. Kev siv concentration feem ntau yog 2.0% -20%.
4.2 raws li ib tug binder thiab disintegrant
Cov qib qis viscosity ntawm cov khoom no tuaj yeem siv los ua ib qho kev sib khi thiab disintegrant rau cov ntsiav tshuaj, tshuaj, thiab granules, thiab qib high-viscosity tsuas yog siv los ua cov ntawv khi. Qhov ntau npaum li cas sib txawv nrog cov qauv sib txawv thiab cov kev xav tau. Feem ntau, tus nqi ntawm cov binder siv rau cov ntsiav tshuaj qhuav granulation yog 5%, thiab tus nqi ntawm cov binder siv rau cov ntsiav tshuaj ntub dej yog 2%.
4.3 Raws li tus neeg sawv cev ncua
Suspending tus neeg sawv cev yog viscous gel tshuaj nrog hydrophilicity. Kev siv cov tshuaj tshem tawm hauv kev tshem tawm tus neeg sawv cev tuaj yeem ua rau qeeb qeeb ntawm cov sedimentation ntawm cov khoom, thiab nws tuaj yeem txuas rau saum npoo ntawm cov khoom los tiv thaiv cov khoom los ntawm polymerizing thiab condensing rau hauv ib pawg. Suspending agents ua lub luag haujlwm tseem ceeb hauv kev tsim cov tshuaj ncua. HPMC yog ib qho zoo heev ntawm cov neeg ua haujlwm tshem tawm. Cov tshuaj colloidal yaj rau hauv nws tuaj yeem txo qhov nro ntawm cov kua-cov khoom sib txuas thiab lub zog dawb ntawm cov khoom me me, yog li txhim kho qhov ruaj khov ntawm cov txheej txheem sib txawv. Cov khoom no yog high-viscosity suspension kua npaj ua tus neeg sawv cev ncua. Nws muaj cov nyhuv suspending zoo, yooj yim rau redisperse, tsis nplaum, thiab nplua flocculated hais. Qhov nyiaj ib txwm yog 0.5% mus rau 1.5%.
4.4 Siv los ua cov blocker, qeeb thiab tswj kev tso tawm tus neeg sawv cev thiab tus pore-forming agent
Cov qib high-viscosity ntawm cov khoom no yog siv los npaj hydrophilic gel matrix sustained-tso ntsiav tshuaj, retarders thiab tswj-tso cov neeg ua haujlwm rau cov khoom sib xyaw matrix sustained-tso ntsiav tshuaj. Nws muaj cov nyhuv ntawm ncua kev tso tshuaj. Nws siv concentration yog 10% ~ 80% (W / W). Cov qib qis viscosity yog siv los ua tus neeg sawv cev pore-forming rau sustained lossis tswj kev tso tawm formulations. Cov koob tshuaj thawj zaug uas xav tau rau kev kho cov nyhuv ntawm hom ntsiav tshuaj no tuaj yeem ncav cuag sai, thiab tom qab ntawd cov txiaj ntsig los yog tswj kev tso tawm yog exerted, thiab cov ntshav cov tshuaj concentration yog tswj nyob rau hauv lub cev. Hypromellose hydrates los tsim ib txheej gel thaum nws ntsib nrog dej. Cov txheej txheem ntawm cov tshuaj tso tawm los ntawm cov ntsiav tshuaj matrix feem ntau yog qhov diffusion ntawm gel txheej thiab yaig ntawm gel txheej.
4.5 Cov kua nplaum tiv thaiv siv los ua thickener thiab colloid
Thaum cov khoom no yog siv los ua cov thickener, cov concentration ib txwm yog 0.45% ~ 1.0%. Cov khoom no tuaj yeem ua rau kom muaj kev ruaj ntseg ntawm cov kua nplaum hydrophobic, tsim ib qho kev tiv thaiv colloid, tiv thaiv particle coalescence thiab agglomeration, yog li inhibiting qhov tsim ntawm sediments. Nws cov concentration ib txwm yog 0.5% ~ 1.5%.
4.6 Siv los ua cov khoom siv tshuaj ntsiav
Feem ntau, cov khoom siv ntawm lub plhaub capsule ntawm cov tshuaj ntsiav yog tsuas yog gelatin. Cov txheej txheem tsim khoom ntawm Ming capsule plhaub yog qhov yooj yim, tab sis muaj qee qhov teeb meem thiab tshwm sim xws li kev tiv thaiv tsis zoo ntawm cov dej noo thiab cov pa oxygen rhiab heev, txo cov tshuaj tawg, thiab ncua sijhawm ntawm kev tawg ntawm lub plhaub capsule thaum khaws cia. Yog li, hypromellose yog siv los hloov cov khoom siv tshuaj ntsiav hauv kev npaj cov tshuaj ntsiav, uas txhim kho cov pwm thiab siv cov nyhuv ntawm cov tshuaj ntsiav, thiab tau nthuav dav hauv tsev thiab txawv teb chaws.
4.7 Raws li bioadhesive
Bioadhesive technology, daim ntawv thov ntawm excipients nrog bioadhesive polymers, los ntawm adhering mus rau lub lom mucosa, txhim khu kev txuas ntxiv thiab nruj ntawm kev sib cuag ntawm kev npaj thiab cov mucosa, thiaj li hais tias cov tshuaj maj mam tso tawm thiab absorbed los ntawm lub mucosa kom ua tiav lub hom phiaj ntawm kev kho mob. Nws yog dav siv tam sim no Nws yog siv los kho cov kab mob ntawm qhov ntswg kab noj hniav thiab qhov ncauj mucosa. Gastrointestinal bioadhesion thev naus laus zis yog hom tshiab ntawm kev xa tshuaj uas tsim tawm hauv xyoo tas los no. Nws tsis tsuas yog ncua lub sijhawm nyob ntawm kev npaj tshuaj hauv plab hnyuv, tab sis kuj txhim kho kev sib cuag ntawm cov tshuaj nrog cov cell membrane ntawm qhov chaw nqus thiab hloov cov fluidity ntawm cov cell membrane. Lub zog nkag mus ntawm cov tshuaj mus rau cov hlwb epithelial ntawm cov hnyuv me yog txhim kho, yog li txhim kho bioavailability ntawm cov tshuaj.
4.8 Raws li cov tshuaj pleev ib ce
Raws li kev npaj nplaum rau ntawm daim tawv nqaij, gel muaj ntau yam zoo xws li kev nyab xeeb, kev zoo nkauj, kev tu yooj yim, tus nqi qis, txheej txheem kev npaj yooj yim, thiab kev sib raug zoo nrog cov tshuaj. Nyob rau hauv xyoo tas los no, nws tau txais kev saib xyuas dav thiab tau dhau los ua kev txhim kho ntawm daim tawv nqaij kev npaj sab nraud. kev taw qhia.
4.9 Raws li nag lossis daus inhibitor hauv emulsification system
Post lub sij hawm: Dec-16-2021