Pharmaceutical Sustained-release Excipients

01 Cellulose ether

Cellulose inogona kupatsanurwa kuita ether imwechete uye yakasanganiswa ethers zvichienderana nerudzi rwezvinotsiva. Kune imwe chete yemhando ye substituent mune imwe ether, yakadai semethyl cellulose (MC), ethyl cellulose (EC), hydroxyl Propyl cellulose (HPC), nezvimwewo; panogona kunge paine maviri kana anopfuura anotsiva ether yakasanganiswa, inowanzoshandiswa ndeye hydroxypropyl methyl cellulose (HPMC), ethyl methyl cellulose (EMC), nezvimwewo. Mishonga inoshandiswa mukugadzirwa kwemishonga yepulse-release inomiririrwa nekavhenganiswa ether HPMC, single ether HPC, uye EC, iyo inowanzoshandiswa se disintegrants, kuzvimba agents, retarders, uye mafirimu ekuputira zvinhu.

1.1 Hydroxypropylmethylcellulose (HPMC)

Nekuda kweakasiyana madhigirii ekutsiva methoxy uye hydroxypropyl mapoka, HPMC inowanzo kupatsanurwa kuva marudzi matatu kunze kwenyika: K, E uye F. Pakati pawo, iyo K yakatevedzana ine inokurumidza hydration sipidhi uye inokodzera senge skeleton zvinhu zvekuchengetedza uye kudzorwa. kusunungurwa gadziriro. Iri zvakare pulse release agent. Imwe yezvinonyanya kushandiswa zvinodhaka zvinotakura mumishonga yekugadzirira. HPMC imvura inonyungudika isiri-ionic cellulose ether, hupfu chena, isinganakidze, isinganhuhwi uye isina chepfu, uye inoburitswa pasina shanduko mumuviri wemunhu. Iyo haina kunyungudika mumvura inopisa inopfuura 60°C uye anogona kuzvimba chete; apo zvinobva zvaro zvine viscosities zvakasiyana zvakasanganiswa muzvikamu zvakasiyana, hukama hwemutsara hwakanaka, uye gel yakaumbwa inogona kunyatso kudzora kupararira kwemvura uye kusunungurwa kwezvinodhaka.

HPMC ndechimwe chezvinhu zvinowanzo shandiswa zvepolymer zvichibva mukuzvimba kana kukukurwa kunodzorwa nemishonga yekuburitsa zvinodhaka mune pulse release system. Kuzvimba kuburitswa kwemishonga ndeyekugadzira inoshanda mishonga yemishonga mumapiritsi kana mapellets, uyezve akawanda-layer coating, iyo yekunze layer ndeye Mvura-isina kunyungudika asi mvura-inopindika polymer coating, iyo yemukati layer ipolymer ine kuzvimba kugona, kana mvura ichipinda mukati. iyo yemukati layer, kuzvimba kuchaita kudzvanywa, uye mushure menguva yakati rebei, mushonga unenge wazvimba nekudzorwa kuburitsa mushonga; ukuwo erosion kuburitsa mushonga uri kuburikidza nepakati mushonga pasuru. Kupfekedza nemvura-insoluble kana erosion polymers, kugadzirisa ukobvu hwekuputira kudzora nguva yekuburitsa zvinodhaka.

Vamwe vaongorori vakaferefeta kuburitswa nekuwedzera hunhu hwemapiritsi zvichibva pahydrophilic HPMC, uye vakawana kuti chiyero chekuburitsa chinononoka kakapetwa kashanu pane icho chemapiritsi akajairwa uye ane kuwedzera kukuru.

Zvichiri nemuongorori wekushandisa pseudoephedrine hydrochloride semushonga wemuenzaniso, kutora nzira yakaoma yekuputira, gadzira jasi rejasi neHPMC yemaviscosities akasiyana, gadzirisa kuburitswa kwemushonga. Mhedzisiro yezviyedzo zve vivo yakaratidza kuti pasi pehukobvu hwakafanana, yakaderera-viscosity HPMC inogona kusvika peak concentration mu5h, nepo high-viscosity HPMC yakasvika peak concentration mune dzinenge 10h. Izvi zvinoratidza kuti kana HPMC ichishandiswa sechinhu chekuputira, viscosity yayo ine zvakanyanya kukosha pakuburitsa zvinodhaka.

Vatsvakurudzi vakashandisa verapamil hydrochloride semushonga wemushonga kugadzirira mahwendefa maviri-pulse matatu-layer tablet core cup, uye vakaongorora madhasi akasiyana eHPMC K4M (15%, 20%, 25%, 30%, 35%, w/w; 4M. inoreva mhedzisiro ye viscosity (4000 centipoise) pane yakarebesa nguva Mhedzisiro inoratidza kuti nekuwedzera kwehuwandu hweHPMC K4M, iyo lag yenguva inoiswa pa4 kusvika maawa mashanu, saka iyo HPMC K4M zvemukati zvakatemerwa kuve 25%. Izvi zvinoratidza kuti HPMC inogona kunonoka kuburitswa kwemushonga wepakati nekudzivirira kuti mushonga usabatane nemvura uye kuita basa mukuburitswa kunodzorwa.

1.2 Hydroxypropylcellulose (HPC)

HPC inogona kukamurwa kuita yakaderera-inotsiva hydroxypropyl cellulose (L-HPC) uye yakakwirira-inotsiva hydroxypropyl cellulose (H-HPC). L-HPC haina-ionic, chena kana isina-chena poda, isinganhuhwi uye isinganakidze, uye iripakati Non-chepfu cellulose zvinobva kune zvisingakuvadze kumuviri wemunhu. Nekuti L-HPC ine nzvimbo yakakura yepasi uye porosity, inogona kukurumidza kutora mvura nekuzvimba, uye kuwedzera kwayo kwekuwedzera kwemvura ndeye 500-700%. Pinda muropa, saka inogona kukurudzira kusunungurwa kwechirwere mu-multi-layer tablet uye pellet core, uye inovandudza zvikuru kurapa.

Mune mahwendefa kana pellets, kuwedzera L-HPC kunobatsira piritsi core (kana pellet core) kuti riwedzere kuburitsa simba remukati, iro rinotyora coating layer uye kuburitsa mushonga mukupuruzira. Vatsvakurudzi vakashandisa sulpiride hydrochloride, metoclopramide hydrochloride, diclofenac sodium, uye nilvadipine semishonga yemuenzaniso, uye yakaderera-inotsiva hydroxypropyl cellulose (L-HPC) senhengo inoparadza. Izvo zviedzo zvakaratidza kuti ukobvu hwekuzvimba layer hunotaridza saizi yechikamu. nguva yekunonoka.

Vatsvakurudzi vakashandisa antihypertensive mishonga sechinhu chekudzidza. Mukuedza, L-HPC yaivepo mumapiritsi uye capsules, kuitira kuti inotora mvura uye yobva yanyura kuburitsa mushonga nekukurumidza.

Vatsvakurudzi vakashandisa terbutaline sulfate pellets semushonga wemuenzaniso, uye migumisiro yekutanga yekuedza yakaratidza kuti kushandisa L-HPC sechinhu chemukati wekuputira denga uye kuwedzera SDS yakakodzera kune yemukati yekuputira layer inogona kuwana inotarisirwa pulse release effect.

1.3 Ethyl cellulose (EC) uye yayo aqueous dispersion (ECD)

EC isiri-ionic, mvura-insoluble cellulose alkyl ether, iyo ine maitiro ekupikisa kwemakemikari, kusanzwa kwemunyu, alkali kupikisa uye kugadzikana kwekupisa, uye ine zvakasiyana-siyana zve viscosity (molecular weight) uye kushanda kwakanaka kwembatya, inogona kuita coating layer nekusimba kwakanaka uye haisi nyore kupfeka, izvo zvinoita kuti ishandiswe zvakanyanya mumishonga inotsigirwa uye inodzorwa kuburitsa firimu coating.

ECD is a heterogeneous system umo ethyl cellulose inoturikwa mu dispersant (mvura) muchimiro chediki colloidal particles uye ine yakanaka kugadzikana kwemuviri. Mvura yakanyunguduka polymer inoshanda sepore-forming agent inoshandiswa kugadzirisa kusunungurwa kweECD kuti ienderane nezvinodiwa zvekuchengetedzwa kwakasimba kwemishonga yekugadzirira kusunungurwa-kusunungurwa.

EC chinhu chakanakira kugadzirwa kweasina-mvura-soluble capsules. Vatsvakurudzi vakashandisa dichloromethane/absolute ethanol/ethyl acetate (4/0.8/0.2) se solvent uye EC (45cp) kugadzirira 11.5% (w/v) EC solution , kugadzirira EC capsule body, uye kugadzirira iyo isiri permeable EC capsule. kusangana nezvinodiwa zvekuburitsa pulse yemuromo. Vatsvakurudzi vakashandisa theophylline semushonga wemuenzaniso wekudzidza kugadzirwa kwemultiphase pulse system yakavharwa ne ethyl cellulose aqueous dispersion. Mhedzisiro yakaratidza kuti mhando yeAquacoat® muECD yakanga isina kusimba uye iri nyore kutyoka, kuve nechokwadi chekuti mushonga waigona kuburitswa mumhepo.

Pamusoro pezvo, vaongorori vakaongorora mapereti anodzorwa nepulse akagadzirwa ne ethyl cellulose aqueous dispersion seyekunze yekuvharisa layer. Kana huremu hweiyo yekunze yekupfekedza layer yaive 13%, iyo yakawedzera kuburitswa kwezvinodhaka yakawanikwa nekurebesa kwenguva kwe5 h uye nguva ye1.5 h. Kupfuura 80% ye pulse release effect.

02 Acrylic resin

Acrylic resin imhando yepolymer mukomboni wakagadzirwa necopolymerization ye acrylic asidhi uye methacrylic acid kana esters avo mune imwe chikamu. Iyo inowanzo shandiswa acrylic resin ndeye Eudragit sezita rayo rekutengesa, ine yakanaka-yekugadzira firimu zvinhu uye ine mhando dzakasiyana senge gastric-soluble E type, enteric-soluble L, S mhando, uye mvura-insoluble RL neRS. Nekuti Eudragit ine mabhenefiti eakanakisa ekugadzira firimu kuita uye kuenderana kwakanaka pakati pemhando dzakasiyana siyana, yakashandiswa zvakanyanya mukuputira firimu, kugadzirira matrix, microspheres uye mamwe pulse kuburitsa masisitimu.

Vatsvakurudzi vakashandisa nitrendipine semushonga wemuenzaniso uye Eudragit E-100 semubatsiri anokosha kugadzirira pH-sensitive pellets, uye akaongorora bioavailability yavo mumbwa dzine utano. Mhedzisiro yechidzidzo ichi yakawana kuti matatu-dimensional chimiro cheEudragit E-100 inoita kuti iburitswe nekukurumidza mukati memaminitsi makumi matatu pasi pemamiriro eacidic. Kana ma pellets ari papH 1.2, nguva yasara imaawa maviri, papH 6.4, nguva yasara maawa maviri, uye papH 7.8, nguva yasara maawa matatu, ayo anogona kuona kudzora kuburitswa mudumbu.

Vatsvakurudzi vakaita zviyero zve9: 1, 8: 2, 7: 3 uye 6: 4 pane zvigadzirwa zvekugadzira firimu Eudragit RS uye Eudragit RL zvakateerana, uye vakaona kuti nguva yakasara yaive 10h apo reshiyo yaive 9: 1. , uye nguva yakanonoka yaive 10h apo reshiyo yaive 8:2. Nguva inononoka ndeye 7h pa2, nguva ye7: 3 i5h, uye nguva ye6: 4 i2h; kune porogens Eudragit L100 uye Eudragit S100, Eudragit L100 inogona kuzadzisa chinangwa chepulse che5h nguva lag mu pH5-7 nharaunda; 20%, 40% uye 50% yemhinduro yekuputira, zvakaonekwa kuti iyo yekuputira mhinduro ine 40% EudragitL100 inogona kusangana neiyo nguva lag inodiwa; mamiriro ari pamusoro apa anogona kuzadzisa chinangwa chenguva ye5.1 h pa pH 6.5 uye nguva yekubuda kwepulse yemaawa matatu.

03 Polyvinylpyrrolidones (PVP)

PVP isiri-ionic mvura-inonyungudika polima musanganiswa wakagadzirwa kubva kuN-vinylpyrrolidone (NVP). Yakakamurwa kuita mamakisi mana maererano neavhareji yaro molecular uremu. Inowanzo kuratidzwa neK kukosha. Iyo yakakura viscosity, iyo yakasimba yekunamatira. PVP gel (upfu) ine simba rekushambadza mhedzisiro pamishonga yakawanda. Mushure mekupinda mudumbu kana muropa, nekuda kweiyo yakanyanya kuzvimba pfuma, mushonga unoburitswa zvishoma nezvishoma. Inogona kushandiswa seyakanakisa inotsigirwa inoburitsa mumiriri muPDDS.

Verapamil pulse osmotic tablet ipiritsi matatu-layer osmotic pombi, iyo yemukati inogadzirwa ne hydrophilic polymer PVP seyo push layer, uye iyo hydrophilic substance inoumba hydrophilic gel kana ikasangana nemvura, iyo inodzoreredza kuburitswa kwezvinodhaka, inowana nguva, uye. inosundira Iyo layer inozvimba zvakanyanya kana ikasangana nemvura, ichisundira mushonga kunze kwegomba rekuburitsa, uye iyo osmotic pressure propellant ndiyo kiyi yekubudirira kwekuumbwa.

Vatsvakurudzi vakashandisa verapamil hydrochloride inodzorwa-yakasunungurwa mahwendefa semishonga yemuenzaniso, uye vakashandisa PVP S630 uye PVP K90 ine viscosities yakasiyana-siyana seyakagadziriswa-yakasunungurwa yekuputira zvinhu. Kana iyo firimu inorema inosvika 8%, iyo nguva lag (tlag) yekusvika in vitro kuburitswa maawa 3-4, uye avhareji yekuburitsa mwero (Rt) ndeye 20-26 mg / h.

04 Hydrogel

4.1. Alginic acid

Alginic asidhi chena kana yakareruka yero poda, isinganhuhwi uye haina kunaka, yakasikwa cellulose isinganyunguriki mumvura. Iyo yakapfava sol-gel process uye yakanaka biocompatibility yealginic acid yakakodzera kugadzira microcapsules inoburitsa kana embed zvinodhaka, mapuroteni uye masero - nyowani dosage fomu muPDDS mumakore achangopfuura.

Vatsvakurudzi vakashandisa dextran semuenzaniso wemushonga uye calcium alginate gel semutakuri wezvinodhaka kuti aite gadziriro yepulse. Mhedzisiro Mushonga une huremu hwepamusoro-soro wakaratidza nguva-lag-pulse kusunungurwa, uye nguva yakarembera inogona kugadziriswa nekukora kwefirimu rekuputira.

Vatsvakurudzi vakashandisa sodium alginate-chitosan kugadzira microcapsules kuburikidza ne electrostatic interaction. Maedzo anoratidza kuti iwo mamicrocapsules ane yakanaka pH yekupindura, zero-odha kuburitswa papH = 12, uye pulse kuburitswa papH = 6.8. Iyo yekuburitsa curve Fomu S, inogona kushandiswa senge pH-inopindura pulsatile formulation.

4.2. Polyacrylamide (PAM) nezvinobvamo

PAM uye zvinobva pairi imvura-inonyungudika yakakwira mapolymers, ayo anonyanya kushandiswa mune pulse release system. Iyo inopisa-sensitive hydrogel inogona kudzoreredza kuwedzera uye kubvisa-kuwedzera (kuderera) nekuchinja kwekunze tembiricha, zvichikonzera shanduko yepermeability, nekudaro Kuzadzisa chinangwa chekudzora kuburitswa kwezvinodhaka.

Iyo yakanyanya kudzidzwa ndeyeN-isopropylacrylamide (NIPAAm) hydrogel, ine yakakosha kunyungudika (LCST) ye32.°C. Kana tembiricha yakakwira kupfuura LCST, gel inodzikira, uye iyo inonyungudutsa mumambure maitiro inosvinwa kunze, ichiburitsa huwandu hukuru hweDrug-containing aqueous solution; kana tembiricha yadzikira pane LCST, iyo gel inogona kuzvimba zvakare, uye tembiricha yekunzwa kweNPAAm gel inogona kushandiswa kugadzirisa kuzvimba maitiro, saizi yegel, chimiro, nezvimwe kuti uwane chaiyo "on-off" kuburitsa zvinodhaka tembiricha uye Zvinodhaka zvinoburitswa mwero thermosensitive hydrogel pulsatile inodzorwa kuburitsa kuumbwa.

Vatsvakurudzi vakashandisa musanganiswa wekushisa-sensitive hydrogel (N-isopropylacrylamide) uye superferric iron tetroxide particles sechinhu. Iyo network maitiro eiyo hydrogel inoshandurwa, nekudaro ichimhanyisa kuburitswa kwezvinodhaka uye kuwana mhedzisiro yekubuda kwepulse.

05 mamwe mapoka

Pamusoro pekushandiswa kwakapararira kwezvinhu zvechinyakare zvepolymer zvakaita seHPMC, CMS-Na, PVP, Eudragit, uye Surlease, zvimwe zvinhu zvitsva zvinotakura zvakaita sechiedza, magetsi, magineti, mafungu e ultrasonic, uye nanofibers zvakaramba zvichigadzirwa. Semuenzaniso, sonic-sensitive liposome inoshandiswa semutakuri wezvinodhaka nevatsvakurudzi, uye kuwedzerwa kwemafungu e ultrasonic kunogona kuita zvishoma zvegesi mu sonic-sensitive liposome kufamba, kuitira kuti mushonga usunungurwe nokukurumidza. Maelectrospun nanofibers akashandiswa nevatsvakurudzi muTPPS neChroB kugadzira modhi yemhando ina-layer, uye kuburitswa kwepulse kwaigona kuitika mune inofananidzirwa muvivo nharaunda ine mazana mashanu.μg/ml protease, 50mM hydrochloric acid, pH8.6.