Pharmaceutical Sustained-release Excipients

01 Cellulose ether

Cellulose tuaj yeem muab faib ua ib leeg ethers thiab sib xyaw ethers raws li hom kev hloov pauv. Tsuas muaj ib hom kev hloov pauv hauv ib qho ether, xws li methyl cellulose (MC), ethyl cellulose (EC), hydroxyl Propyl cellulose (HPC), thiab lwm yam; tuaj yeem muaj ob lossis ntau qhov hloov pauv hauv cov ether sib xyaw, feem ntau siv yog hydroxypropyl methyl cellulose (HPMC), ethyl methyl cellulose (EMC), thiab lwm yam. Cov excipients siv nyob rau hauv cov tshuaj pulse-tso tshuaj npaj yog sawv cev los ntawm mixed ether HPMC, ib leeg ether HPC, thiab EC, uas feem ntau yog siv los ua disintegrants, o, o, retarders, thiab zaj duab xis txheej.

1.1 Hydroxypropylmethylcellulose (HPMC)

Vim yog qhov sib txawv ntawm kev hloov pauv ntawm methoxy thiab hydroxypropyl pawg, HPMC feem ntau muab faib ua peb hom txawv teb chaws: K, E thiab F. Ntawm lawv, K series muaj cov dej nrawm tshaj plaws thiab tsim nyog raws li cov khoom siv pob txha rau kev txhawb nqa thiab tswj. tso kev npaj. Nws kuj yog ib tug pulse tso tus neeg sawv cev. Ib qho ntawm feem ntau siv tshuaj nqa khoom hauv kev npaj tshuaj. HPMC yog cov dej-soluble uas tsis yog-ionic cellulose ether, hmoov dawb, tsis qab, tsis muaj ntxhiab thiab tsis muaj tshuaj lom, thiab nws raug tso tawm yam tsis muaj kev hloov pauv hauv tib neeg lub cev. Nws yog qhov yooj yim insoluble hauv dej kub tshaj 60°C thiab tsuas tuaj yeem o; Thaum nws cov derivatives nrog cov viscosities sib txawv sib xyaw ua ke sib txawv, txoj kev sib raug zoo yog qhov zoo, thiab cov gel tsim tuaj yeem tswj tau cov dej ntws tawm thiab tso tshuaj.

HPMC yog ib qho ntawm cov khoom siv polymer uas nquag siv raws li qhov o los yog yaig tswj cov tshuaj tso tawm mechanism hauv pulse tso tawm. Cov tshuaj o uas tso tawm yog los npaj cov khoom xyaw tshuaj nquag rau hauv cov ntsiav tshuaj lossis pellets, thiab tom qab ntawd txheej txheej txheej txheej yog dej-insoluble tab sis dej-permeable polymer txheej, txheej sab hauv yog cov polymer nrog o muaj peev xwm, thaum cov kua nkag mus rau hauv. cov txheej sab hauv, qhov o yuav ua rau lub siab, thiab tom qab lub sijhawm, cov tshuaj yuav o thiab tswj kom tso cov tshuaj; thaum lub erosion tso tshuaj yog los ntawm cov core tshuaj pob. Txheej nrog dej-insoluble los yog yaig polymers, kho cov txheej thickness los tswj cov tshuaj tso tawm lub sij hawm.

Qee cov kws tshawb fawb tau tshawb xyuas qhov kev tso tawm thiab nthuav tawm cov yam ntxwv ntawm cov ntsiav tshuaj raws li hydrophilic HPMC, thiab pom tias qhov kev tso tawm yog 5 npaug qeeb dua li cov ntsiav tshuaj zoo tib yam thiab muaj kev nthuav dav ntau.

Tseem muaj cov kws tshawb fawb siv pseudoephedrine hydrochloride ua qauv tshuaj, txais yuav cov txheej txheem qhuav txheej, npaj txheej txheej nrog HPMC ntawm cov viscosities sib txawv, kho cov tshuaj tso tawm. Cov txiaj ntsig ntawm kev sim vivo tau pom tias nyob rau hauv tib lub thickness, tsawg-viscosity HPMC tuaj yeem ncav cuag qhov siab tshaj plaws hauv 5h, thaum lub siab-viscosity HPMC mus txog qhov siab tshaj plaws hauv li 10h. Qhov no qhia tau hais tias thaum HPMC siv los ua cov khoom siv txheej, nws cov viscosity muaj qhov cuam tshuam loj dua rau tus cwj pwm tso tshuaj.

Cov kws tshawb fawb siv verapamil hydrochloride ua cov qauv tshuaj los npaj ob-pulse peb-txheej ntsiav tshuaj core khob ntsiav tshuaj, thiab tshawb xyuas ntau npaum li cas ntawm HPMC K4M (15%, 20%, 25%, 30%, 35%, w / w; 4M. hais txog cov nyhuv ntawm viscosity (4000 centipoise) ntawm lub sij hawm lag Cov txiaj ntsig tau pom tias nrog kev nce ntawm HPMC K4M, lub sij hawm lag luam yog ncua sij hawm ntawm 4 mus rau 5 teev, yog li HPMC K4M Cov ntsiab lus tau txiav txim siab tias yog 25%.

1.2 Hydroxypropylcellulose (HPC)

HPC tuaj yeem muab faib ua qis-hloov hydroxypropyl cellulose (L-HPC) thiab high-substituted hydroxypropyl cellulose (H-HPC). L-HPC yog non-ionic, dawb los yog off-dawb hmoov, tsw thiab saj, thiab yog nruab nrab Non-toxic cellulose derivatives uas tsis muaj teeb meem rau tib neeg lub cev. Vim tias L-HPC muaj thaj tsam loj thiab qhov porosity, nws tuaj yeem nqus dej sai sai, thiab nws qhov nqus dej nthuav dav yog 500-700%. Nkag mus rau hauv cov ntshav, yog li nws tuaj yeem txhawb kev tso tawm cov tshuaj hauv cov ntsiav tshuaj ntau txheej thiab pellet core, thiab txhim kho cov nyhuv curative zoo heev.

Hauv cov ntsiav tshuaj lossis pellets, ntxiv L-HPC pab cov ntsiav tshuaj (los yog pellet core) kom nthuav dav los tsim kom muaj zog sab hauv, uas ua rau cov txheej txheej txheej thiab tso tawm cov tshuaj hauv cov mem tes. Cov kws tshawb fawb tau siv sulpiride hydrochloride, metoclopramide hydrochloride, diclofenac sodium, thiab nilvadipine ua qauv tshuaj, thiab qis-hloov hydroxypropyl cellulose (L-HPC) ua tus neeg sawv cev disintegrating. Cov kev sim qhia tau hais tias lub thickness ntawm lub o txheej txheej txiav txim siab particle loj. lag sij hawm.

Cov kws tshawb fawb tau siv cov tshuaj tiv thaiv hypertensive raws li kev tshawb fawb. Hauv kev sim, L-HPC muaj nyob rau hauv cov ntsiav tshuaj thiab tshuaj ntsiav, kom lawv nqus dej thiab tom qab ntawd eroded kom tso cov tshuaj sai.

Cov kws tshawb fawb tau siv terbutaline sulfate pellets ua cov qauv tshuaj, thiab qhov kev sim ua ntej tau pom tias siv L-HPC ua cov khoom ntawm txheej txheej sab hauv thiab ntxiv SDS tsim nyog rau cov txheej txheej sab hauv tuaj yeem ua tiav qhov kev cia siab pulse tso tawm.

1.3 Ethyl cellulose (EC) thiab nws cov aqueous dispersion (ECD)

EC yog non-ionic, dej-insoluble cellulose alkyl ether, uas muaj cov yam ntxwv ntawm cov tshuaj tiv thaiv, ntsev tsis kam, alkali tsis kam thiab kub stability, thiab muaj ntau yam viscosity (molecular hnyav) thiab zoo khaub ncaws kev ua tau zoo, muaj peev xwm tsim ib tug ntau yam ntawm viscosity. txheej txheej nrog zoo toughness thiab tsis yooj yim rau hnav, uas ua rau nws lug siv nyob rau hauv cov tshuaj sustained thiab tswj tso tawm zaj duab xis txheej.

ECD yog cov txheej txheem sib txawv uas ethyl cellulose raug tshem tawm hauv cov khoom tawg (dej) hauv daim ntawv me me colloidal hais thiab muaj lub cev zoo. Ib qho dej-soluble polymer uas ua raws li tus neeg sawv cev pore-forming yog siv los kho tus nqi tso tawm ntawm ECD kom ua tau raws li cov kev cai ntawm kev tso tawm tshuaj ntxiv rau kev npaj tso tawm.

EC yog cov khoom siv zoo tshaj plaws rau kev npaj cov tshuaj uas tsis yog dej-soluble capsules. Cov kws tshawb fawb tau siv dichloromethane / absolute ethanol / ethyl acetate (4/0.8/0.2) ua hnyav thiab EC (45cp) los npaj 11.5% (w/v) EC tov, npaj EC capsule lub cev, thiab npaj cov tshuaj uas tsis yog permeable EC capsule. ua tau raws li qhov yuav tsum tau muaj ntawm qhov ncauj pulse tso tawm. Cov kws tshawb fawb tau siv theophylline ua cov qauv tshuaj los kawm txog kev txhim kho ntawm ntau theem pulse system coated nrog ethyl cellulose aqueous dispersion. Cov txiaj ntsig tau pom tias Aquacoat® ntau yam hauv ECD yog qhov tsis yooj yim thiab yooj yim tawg, kom ntseeg tau tias cov tshuaj tuaj yeem tso tawm hauv lub plawv.

Tsis tas li ntawd, cov kws tshawb fawb tau kawm txog cov pulse-tswj tso tawm pellets npaj nrog ethyl cellulose aqueous dispersion raws li txheej txheej txheej. Thaum qhov hnyav nce ntawm txheej txheej txheej yog 13%, cov tshuaj tso tawm tau ua tiav nrog lub sijhawm lag luam ntawm 5 h thiab lub sijhawm lag luam ntawm 1.5 teev. Ntau tshaj 80% ntawm cov nyhuv pulse tso tawm.

02 Acrylic cob

Acrylic resin yog ib hom polymer compound tsim los ntawm copolymerization ntawm acrylic acid thiab methacrylic acid los yog lawv cov esters nyob rau hauv ib qho kev faib ua feem. Feem ntau siv acrylic resin yog Eudragit raws li nws lub npe lag luam, uas muaj cov yeeb yaj kiab zoo thiab muaj ntau yam xws li gastric-soluble E hom, enteric-soluble L, S hom, thiab dej-insoluble RL thiab RS. Vim hais tias Eudragit muaj qhov zoo ntawm kev ua yeeb yaj kiab zoo tshaj plaws thiab kev sib raug zoo ntawm ntau cov qauv, nws tau siv dav hauv cov txheej txheem zaj duab xis, kev npaj matrix, microspheres thiab lwm yam pulse tso tshuab.

Cov kws tshawb fawb tau siv nitrendipine ua qauv tshuaj thiab Eudragit E-100 ua ib qho tseem ceeb excipient los npaj pH-sensitive pellets, thiab ntsuam xyuas lawv bioavailability nyob rau hauv cov dev noj qab nyob zoo. Cov txiaj ntsig ntawm txoj kev tshawb fawb pom tias cov qauv peb-seem ntawm Eudragit E-100 ua rau nws tso tawm sai sai hauv 30 feeb nyob rau hauv cov kua qaub. Thaum cov pellets nyob ntawm pH 1.2, lub sij hawm lag luam yog 2 teev, ntawm pH 6.4, lub sij hawm lag luam yog 2 teev, thiab ntawm pH 7.8, lub sij hawm lag luam yog 3 teev, uas tuaj yeem paub tswj kev tso tawm hauv cov hnyuv.

Cov kws tshawb fawb tau ua tiav qhov sib piv ntawm 9: 1, 8: 2, 7: 3 thiab 6: 4 ntawm cov ntaub ntawv ua yeeb yaj kiab Eudragit RS thiab Eudragit RL feem, thiab pom tias lub sijhawm lag luam yog 10h thaum qhov piv yog 9: 1. , thiab lub sij hawm lag yog 10h thaum piv yog 8: 2. Lub sijhawm lag luam yog 7h ntawm 2, lub sijhawm lag luam ntawm 7: 3 yog 5h, thiab lub sijhawm lag luam ntawm 6: 4 yog 2h; rau porogens Eudragit L100 thiab Eudragit S100, Eudragit L100 tuaj yeem ua tiav lub hom phiaj mem tes ntawm 5h lub sij hawm lag hauv pH5-7 ib puag ncig; 20%, 40% thiab 50% ntawm txheej txheej, nws tau pom tias cov txheej txheem txheej txheem muaj 40% EudragitL100 tuaj yeem ua tau raws li lub sijhawm lag luam xav tau; Cov xwm txheej saum toj no tuaj yeem ua tiav lub hom phiaj ntawm lub sijhawm lag luam ntawm 5.1 h ntawm pH 6.5 thiab lub sijhawm tso tawm mem tes ntawm 3 teev.

03 Polyvinylpyrrolidones (PVP)

PVP yog non-ionic dej-soluble polymer compound polymerized los ntawm N-vinylpyrrolidone (NVP). Nws muab faib ua plaub qib raws li nws qhov nruab nrab molecular hnyav. Nws feem ntau yog qhia los ntawm K tus nqi. Qhov ntau dua qhov viscosity, lub zog adhesion. PVP gel (hmoov) muaj zog adsorption nyhuv ntawm cov tshuaj feem ntau. Tom qab nkag mus rau hauv lub plab los yog cov ntshav, vim nws cov cuab yeej o ntawm lub siab heev, cov tshuaj tso tawm maj mam. Nws tuaj yeem siv los ua tus neeg sawv cev zoo tshaj tawm hauv PDDS.

Verapamil pulse osmotic ntsiav tshuaj yog peb-txheej ntsiav tshuaj osmotic twj tso kua mis, lub puab txheej yog tsim los ntawm hydrophilic polymer PVP raws li lub laub txheej, thiab cov tshuaj hydrophilic tsim ib hydrophilic gel thaum nws ntsib dej, uas retards tshuaj tso tawm, tau lub sij hawm lag, thiab pushes Cov txheej swells zoo thaum nws ntsib dej, thawb cov tshuaj tawm ntawm qhov tso tawm, thiab osmotic siab propellant yog tus yuam sij rau kev ua tiav ntawm kev tsim.

Cov kws tshawb fawb tau siv verapamil hydrochloride tswj-tso ntsiav tshuaj ua qauv tshuaj, thiab siv PVP S630 thiab PVP K90 nrog cov viscosities sib txawv raws li kev tswj-tso txheej txheej. Thaum cov yeeb yaj kiab hnyav nce yog 8%, lub sij hawm lag (tlag) kom ncav cuag hauv vitro tso tawm yog 3-4 teev, thiab qhov nruab nrab tso tawm (Rt) yog 20-26 mg / h.

04 Hydrogel

4.1. Alginic acid

Alginic acid yog dawb los yog lub teeb daj hmoov, tsis muaj ntxhiab thiab tasteless, lub ntuj cellulose insoluble nyob rau hauv dej. Cov txheej txheem me me sol-gel thiab biocompatibility zoo ntawm alginic acid yog tsim nyog rau kev ua microcapsules uas tso tawm los yog embed tshuaj, proteins thiab hlwb - ib tug tshiab npaum li cas daim ntawv nyob rau hauv PDDS nyob rau hauv xyoo tas los.

Cov kws tshawb fawb tau siv dextran ua cov qauv tshuaj thiab calcium alginate gel ua cov neeg nqa tshuaj los ua kev npaj pulse. Cov txiaj ntsig Cov tshuaj uas muaj qhov hnyav molecular tau nthuav tawm lub sijhawm-lag-pulse tso tawm, thiab lub sijhawm lag luam tuaj yeem hloov kho los ntawm cov tuab ntawm txheej zaj duab xis.

Cov kws tshawb fawb siv sodium alginate-chitosan los tsim microcapsules los ntawm kev sib cuam tshuam electrostatic. Cov kev sim qhia tau hais tias cov microcapsules muaj pH zoo teb, xoom xaj tso tawm ntawm pH = 12, thiab mem tes tso tawm ntawm pH = 6.8. Daim ntawv nthuav tawm daim ntawv S, tuaj yeem siv los ua pH-responsive pulsatile formulation.

4.2. Polyacrylamide (PAM) thiab nws cov derivatives

PAM thiab nws cov derivatives yog dej-soluble siab molecular polymers, uas yog tsuas yog siv nyob rau hauv lub pulse tso system. Lub tshav kub-rhiab heev hydrogel tuaj yeem thim rov qab nthuav dav thiab de-expand (shrink) nrog kev hloov pauv ntawm sab nraud kub, ua rau muaj kev hloov pauv hauv permeability, yog li kom ua tiav lub hom phiaj ntawm kev tswj cov tshuaj tso tawm.

Qhov feem ntau kawm yog N-isopropylacrylamide (NIPAAm) hydrogel, nrog rau qhov tseem ceeb melting point (LCST) ntawm 32°C. Thaum qhov kub siab tshaj qhov LCST, cov gel shrinks, thiab cov kuab tshuaj nyob rau hauv lub network qauv yog squeezed tawm, tso ib tug loj npaum li cas ntawm cov tshuaj aqueous tov; Thaum qhov kub thiab txias qis dua LCST, cov gel tuaj yeem rov o, thiab qhov kub thiab txias ntawm NPAAm gel tuaj yeem siv los kho tus cwj pwm o, gel loj, cov duab, thiab lwm yam kom ua tiav qhov "on-off" tshuaj tso tawm kub thiab Cov tshuaj tso tawm tus nqi thermosensitive hydrogel pulsatile tswj kev tso tawm formulation.

Cov kws tshawb fawb tau siv cov khoom sib xyaw ntawm qhov kub thiab txias hydrogel (N-isopropylacrylamide) thiab superferric hlau tetroxide raws li cov khoom siv. Lub network qauv ntawm hydrogel hloov, yog li ua kom cov tshuaj tso tawm sai thiab tau txais cov nyhuv ntawm cov mem tes tso tawm.

05 lwm pawg

Ntxiv nrog rau kev siv ntau yam khoom siv polymer xws li HPMC, CMS-Na, PVP, Eudragit, thiab Surlease, lwm yam khoom siv tshiab xws li lub teeb, hluav taws xob, magnetic teb, ultrasonic tsis, thiab nanofibers tau tsim tas li. Piv txwv li, sonic-sensitive liposome yog siv los ua cov khoom siv tshuaj los ntawm cov kws tshawb fawb, thiab qhov sib ntxiv ntawm ultrasonic nthwv dej tuaj yeem ua rau cov pa me me hauv cov sonic-sensitive liposome txav, kom cov tshuaj tuaj yeem tso tawm sai. Cov electrospun nanofibers tau siv los ntawm cov kws tshawb fawb hauv TPPS thiab ChroB los tsim cov qauv plaub-txheej txheej, thiab cov mem tes tso tawm tuaj yeem pom tau hauv qhov simulated hauv vivo ib puag ncig uas muaj 500.μg/ml protease, 50mM hydrochloric acid, pH 8.6.