Imiti ikomeza-kurekura ibicuruzwa

01 Cellulose ether

Cellulose irashobora kugabanywamo ethers imwe hamwe na ethers ivanze ukurikije ubwoko bwibisimburwa. Hariho ubwoko bumwe gusa bwinsimburangingo muri ether imwe, nka methyl selulose (MC), Ethyl selulose (EC), hydroxyl Propyl selulose (HPC), nibindi.; hashobora kubaho insimburangingo ebyiri cyangwa nyinshi muri ether ivanze, ikunze gukoreshwa ni hydroxypropyl methyl selulose (HPMC), Ethyl methyl selulose (EMC), nibindi. Ibicuruzwa bikoreshwa mugutegura imiti irekura imiti bigereranywa na ether HPMC ivanze, ether imwe ya HPC, na EC, bikunze gukoreshwa nkibidahwitse, imiti yabyimba, retarders, nibikoresho byo gutwikira firime.

1.1 Hydroxypropylmethylcellulose (HPMC)

Bitewe nimpamyabumenyi zitandukanye zo gusimbuza imikorere ya mikorobe na hydroxypropyl, HPMC muri rusange igabanyijemo ubwoko butatu mumahanga: K, E na F. Muri byo, K ikurikirana ifite umuvuduko mwinshi wihuta kandi irakwiriye nkibikoresho bya skeleton kugirango bikomeze kandi bigenzurwe kurekura imyiteguro. Nibikorwa byo kurekura pulse. Umwe mubatwara ibiyobyabwenge cyane mugutegura imiti. HPMC ni amazi ashonga idafite ionic selulose ether, ifu yera, uburyohe, impumuro nziza kandi idafite uburozi, kandi irasohoka nta gihindutse mumubiri wumuntu. Ntibishobora gushonga mumazi ashyushye hejuru ya 60°C kandi irashobora kubyimba gusa; iyo ibiyikomokaho hamwe na viscosité zitandukanye bivanze muburyo butandukanye, umubano wumurongo ni mwiza, kandi gel yakozwe irashobora kugenzura neza ikwirakwizwa ryamazi no kurekura ibiyobyabwenge.

HPMC ni kimwe mu bikoresho bisanzwe bikoreshwa na polymer bishingiye kubyimba cyangwa isuri bigenzurwa no kurekura ibiyobyabwenge muri sisitemu yo kurekura impiswi. Kurekura ibiyobyabwenge kubyimba ni ugutegura ibikoresho bya farumasi bikora mubinini cyangwa pelleti, hanyuma bigashyirwa mubice byinshi, igipande cyinyuma ni Amazi adashobora gushonga ariko amazi yinjizwa mumazi, igipande cyimbere ni polymer ifite ubushobozi bwo kubyimba, mugihe amazi yinjiye. urwego rwimbere, kubyimba bizana umuvuduko, kandi nyuma yigihe runaka, imiti izabyimba kandi igenzurwe kugirango irekure ibiyobyabwenge; mugihe isuri irekura ibiyobyabwenge binyujijwe mumiti yibiyobyabwenge. Gupfundikanya na polimeri idashobora gushonga cyangwa isuri, guhindura umubyimba kugirango ugabanye igihe cyo gusohora ibiyobyabwenge.

Bamwe mu bashakashatsi bakoze ubushakashatsi ku irekurwa no kwaguka biranga ibinini bishingiye kuri hydrophilique HPMC, basanga igipimo cyo gusohora gitinda inshuro 5 ugereranije n’ibinini bisanzwe kandi gifite ubwiyongere bukabije.

Uracyafite abashakashatsi gukoresha hydrochloride ya pseudoephedrine nkumuti wintangarugero, gukoresha uburyo bwo gutwikira bwumye, gutegura ikoti hamwe na HPMC yibibabi bitandukanye, guhindura irekurwa ryimiti. Ibyavuye mu bushakashatsi bwa vivo bwerekanye ko munsi yubunini bumwe, ubukonje buke HPMC bushobora kugera ku gipimo cy’imisozi muri 5h, mu gihe HPMC ifite ubukonje bwinshi yageze ku gipimo cya 10h. Ibi birerekana ko iyo HPMC ikoreshwa nkibikoresho byo gutwikira, ububobere bwayo bugira ingaruka zikomeye kumyitwarire yo kurekura ibiyobyabwenge.

Abashakashatsi bifashishije hydrochloride ya verapamil nk'umuti w'icyitegererezo mu gutegura ibinini bibiri by'ibinini byibinini byibinini bitatu, hanyuma bakora iperereza ku ngano zitandukanye za HPMC K4M (15%, 20%, 25%, 30%, 35%, w / w; 4M bivuga ingaruka za viscosity (4000 centipoise) kumwanya utinze. Ibisubizo byerekana ko hamwe no kwiyongera kwinshi kwa HPMC K4M, igihe cyigihe kirekire ibiyirimo byiyemeje kuba 25%.

1.2 Hydroxypropylcellulose (HPC)

HPC irashobora kugabanywamo hydroxypropyl selulose (L-HPC) hamwe na hydroxypropyl selulose isimbuwe cyane (H-HPC). L-HPC ntabwo ari ionic, ifu yera cyangwa yera-ifu yera, idafite impumuro nziza kandi itaryoshye, kandi ni ibikomoka kuri selile idafite ubumara butagira ubumara bwangiza umubiri wumuntu. Kuberako L-HPC ifite ubuso bunini nubushuhe, irashobora kwinjiza vuba amazi ikabyimba, kandi umuvuduko wo kwaguka kwayo ni 500-700%. Kwinjira mu maraso, bityo birashobora guteza imbere irekurwa ryibiyobyabwenge muri tablet nyinshi hamwe na pellet core, kandi bigatera imbere cyane ingaruka zo kuvura.

Mu bisate cyangwa pellet, kongeramo L-HPC bifasha ibinini bya tablet (cyangwa pellet core) kwaguka kugirango bitange imbaraga zimbere, zimena igipfundikizo kandi zirekura ibiyobyabwenge mumitsi. Abashakashatsi bifashishije hydrochloride ya sulpiride, hydrochloride ya metoclopramide, sodium ya diclofenac, na nilvadipine nk'imiti ntangarugero, hamwe na hydroxypropyl selulose (L-HPC) isimburwa na buke. Ubushakashatsi bwerekanye ko ubunini bwikibyimba bugena ingano yubunini. igihe.

Abashakashatsi bakoresheje imiti igabanya ubukana nk'ikintu cyo kwiga. Mu bushakashatsi, L-HPC yari ihari mu bisate na capsules, ku buryo byinjiza amazi hanyuma bikangirika kugira ngo irekure vuba.

Abashakashatsi bifashishije pelberi ya terbutaline sulfate nk'umuti w'icyitegererezo, kandi ibisubizo by'ibizamini by'ibanze byagaragaje ko gukoresha L-HPC nk'ibikoresho byo mu gifu cy'imbere ndetse no kongeramo SDS ikwiye ku gipimo cy'imbere bishobora kugera ku ngaruka ziteganijwe kurekurwa.

1.3 Ethyl selulose (EC) no gutatanya amazi yayo (ECD)

EC ni ionic, amazi-adashobora gushonga selulose alkyl ether, ifite ibiranga imiti irwanya imiti, kurwanya umunyu, kurwanya alkali hamwe nubushyuhe bukabije, kandi ifite ubwinshi bwimitsi (uburemere bwa molekile) nibikorwa byiza byimyambaro, birashobora gukora a coating layer hamwe nubukomezi bwiza kandi ntabwo byoroshye kwambara, bigatuma ikoreshwa cyane mubiyobyabwenge bikomeza kandi bigenzurwa na firime.

ECD ni uburyo butandukanye aho Ethyl selulose ihagarikwa mugutatanya (amazi) muburyo buto bwa colloidal kandi bifite umubiri mwiza. Amazi ashonga polymer akora nkibikoresho byo gukora pore ikoreshwa muguhindura igipimo cyo kurekura ECD kugirango yuzuze ibisabwa kugirango irekurwa ryibiyobyabwenge rihoraho kugirango imyiteguro irekure irekure.

EC nibikoresho byiza byo gutegura capsules zidafite amazi. Abashakashatsi bakoresheje dichloromethane / etanol absolute / etyl acetate (4 / 0.8 / 0.2) nka solvent na EC (45cp) kugirango bategure igisubizo cya 11.5% (w / v) EC, bategure umubiri wa capsule ya EC, kandi bategure capsule ya EC itemewe. kuzuza ibisabwa byo kurekura umunwa. Abashakashatsi bifashishije theophylline nk'umuti w'icyitegererezo kugira ngo bige ku iterambere rya sisitemu yo mu bwoko bwa pulse ifatanije na Ethyl selulose yo mu mazi. Ibisubizo byerekanye ko ubwoko bwa Aquacoat® muri ECD bwari bworoshye kandi bworoshye kumeneka, byemeza ko imiti ishobora kurekurwa.

Byongeye kandi, abashakashatsi bakoze ubushakashatsi kuri pellet irekurwa na pullet yateguwe hamwe na Ethyl selulose yo mu mazi ikwirakwizwa nkurwego rwo hanze. Iyo kwiyongera k'uburemere bw'igipfukisho cyo hanze cyari 13%, irekurwa ry'ibiyobyabwenge ryagezweho hamwe nigihe cya 5 h hamwe nigihe cya 1.5 h. Kurenga 80% yingaruka zo kurekura.

02 Acrylic resin

Acrylic resin ni ubwoko bwa polymer compound ikorwa na copolymerisation ya acide acrylic na acide methacrylic cyangwa est est zabo muburyo runaka. Ubusanzwe acrylic resin ni Eudragit nkizina ryayo ryubucuruzi, ifite imiterere myiza yo gukora firime kandi ifite ubwoko butandukanye nkubwoko bwa gastric-soluble E, enteric-soluble L, S, hamwe na RL na RS. Kuberako Eudragit afite ibyiza byo gukora firime nziza cyane no guhuza neza muburyo butandukanye, yakoreshejwe cyane mugutunganya firime, gutegura matrix, microsperes hamwe nubundi buryo bwo gusohora pulse.

Abashakashatsi bifashishije nitrendipine nk'umuti w'icyitegererezo na Eudragit E-100 nk'igikoresho gikomeye cyo gutegura pellet zumva pH, banasuzuma bioavailable zabo ku mbwa nzima. Ibyavuye mu bushakashatsi byagaragaje ko imiterere y’ibice bitatu bya Eudragit E-100 ituma irekurwa vuba mu minota 30 mu bihe bya aside. Iyo pellet ziri kuri pH 1.2, igihe cyo gutinda ni amasaha 2, kuri pH 6.4, igihe cyo gutinda ni amasaha 2, naho kuri pH 7.8, igihe cyo gutinda ni amasaha 3, gishobora kumenya ubuyobozi bwo kurekura bugenzurwa mumitsi y amara.

Abashakashatsi bakoze ibipimo bya 9: 1, 8: 2, 7: 3 na 6: 4 ku bikoresho byo gukora filime Eudragit RS na Eudragit RL, basanga igihe cyatinze cyari 10h igihe igipimo cyari 9: 1 , kandi igihe cyatinze cyari 10h mugihe igipimo cyari 8: 2. Igihe cyo gutinda ni 7h kuri 2, igihe kiri 7: 3 ni 5h, naho igihe kiri 6: 4 ni 2h; kuri porogène Eudragit L100 na Eudragit S100, Eudragit L100 irashobora kugera ku ntego ya pulse yigihe cya 5h itinda mubidukikije pH5-7; 20%, 40% na 50% yumuti wo gutwikira, byagaragaye ko igisubizo cyo gutwikira kirimo 40% EudragitL100 gishobora kuzuza igihe cyateganijwe; ibintu byavuzwe haruguru birashobora kugera ku ntego yigihe kinini cya 5.1 h kuri pH 6.5 nigihe cyo kurekura pulse yamasaha 3.

03 Polyvinylpyrrolidone (PVP)

PVP ni ionic water-soluble polymer compound polymerized kuva N-vinylpyrrolidone (NVP). Igabanijwemo ibyiciro bine ukurikije uburemere bwacyo bwa molekile. Mubisanzwe bigaragazwa na K agaciro. Nubunini bwijimye, niko gukomera gukomera. PVP gel (ifu) igira ingaruka zikomeye za adsorption kumiti myinshi. Nyuma yo kwinjira mu gifu cyangwa mu maraso, kubera ibintu byinshi byabyimbye cyane, imiti irekurwa buhoro. Irashobora gukoreshwa nkumukozi mwiza wo kurekura muri PDDS.

Verapamil pulse osmotic tablet ni ibipande bitatu bya pompe osmotic, igipande cyimbere gikozwe muri hydrophilique polymer PVP nkigice cyo gusunika, kandi hydrophilique ikora gel hydrophilique iyo ihuye namazi, ikabuza gusohora ibiyobyabwenge, ikabona igihe, kandi gusunika Igice kibyimba cyane iyo gihuye n’amazi, gusunika ibiyobyabwenge mu mwobo urekura, kandi moteri ya osmotic moteri ni urufunguzo rwo gutsinda neza.

Abashakashatsi bifashishije ibinini bya hydrochloride ya verapamil bigenzurwa-bisohora nk'ibiyobyabwenge by'icyitegererezo, kandi bakoresheje PVP S630 na PVP K90 bafite ibishishwa bitandukanye nk'ibikoresho byo gutwikira. Iyo kwiyongera kwa firime ari 8%, igihe cyo gutinda (tlag) cyo kugera muri vitro irekura ni amasaha 3-4, naho impuzandengo yo gusohora (Rt) ni 20-26 mg / h.

04 Hydrogel

4.1. Acide ya Alginic

Acide ya Alginic ni ifu yera cyangwa yoroheje yumuhondo, impumuro nziza kandi itaryoshye, selile naturel idashobora gushonga mumazi. Inzira yoroheje ya sol-gel hamwe na biocompatibilité nziza ya acide ya alginic irakwiriye gukora microcapsules irekura cyangwa igashyiramo imiti, proteyine na selile - uburyo bushya bwa dosiye muri PDDS mumyaka yashize.

Abashakashatsi bakoresheje dextran nk'umuti w'icyitegererezo na calcium alginate gel nk'itwara ry'ibiyobyabwenge kugirango bategure pulse. Ibisubizo Umuti ufite uburemere buke bwa molekile werekanye igihe-cyo-gusohora, kandi igihe gishobora guhinduka bitewe nubunini bwa firime.

Abashakashatsi bifashishije sodium alginate-chitosan mu gukora microcapsules binyuze mu mikoranire ya electrostatike. Ubushakashatsi bwerekana ko microcapsules ifite pH nziza yo kwitabira, gusohora zeru kuri pH = 12, no gusohora pulse kuri pH = 6.8. Kurekura umurongo Ifishi S, irashobora gukoreshwa nka pH-yitabira pulsatile.

4.2. Polyacrylamide (PAM) n'ibiyikomokaho

PAM n'ibiyikomokaho ni amazi ya elegitoronike ya molekile polymers, ikoreshwa cyane muri sisitemu yo kurekura impiswi. Hydrogel yorohereza ubushyuhe irashobora kwaguka no kwaguka (kugabanuka) hamwe n’imihindagurikire y’ubushyuhe bwo hanze, bigatera ihinduka ry’imikorere, bityo Kugera ku ntego yo kugenzura irekurwa ry’ibiyobyabwenge.

Ubushakashatsi bwakozwe cyane ni N-isopropylacrylamide (NIPAAm) hydrogel, hamwe ningingo ikomeye yo gushonga (LCST) ya 32°C. Iyo ubushyuhe buri hejuru ya LCST, gel iragabanuka, hamwe na solve mumiterere y'urusobekerane, ikarekura umubare munini wibiyobyabwenge birimo ibiyobyabwenge; iyo ubushyuhe buri munsi ya LCST, gel irashobora kongera kubyimba, kandi ubushyuhe bwubushyuhe bwa gel NPAAm burashobora gukoreshwa muguhindura imyitwarire yo kubyimba, ingano ya gel, imiterere, nibindi kugirango ugere kubushyuhe bwa "on-off" bwo kurekura ibiyobyabwenge kandi Igipimo cyo kurekura ibiyobyabwenge thermosensitive hydrogel pulsatile yagenzuwe kurekura.

Abashakashatsi bifashishije hydrogel (N-isopropylacrylamide) yubushyuhe bukabije hamwe na tetroxide ya fer ya superfricique nkibikoresho. Imiterere y'urusobe rwa hydrogel irahindurwa, bityo byihutisha gusohora ibiyobyabwenge no kubona ingaruka zo kurekura impiswi.

Ibindi byiciro 05

Usibye gukoresha cyane ibikoresho bya polymer gakondo nka HPMC, CMS-Na, PVP, Eudragit, na Surlease, ibindi bikoresho bishya bitwara nk'umucyo, amashanyarazi, imirima ya magneti, imiraba ya ultrasonic, na nanofibers byakomeje gutezwa imbere. Kurugero, liposome yunvikana ya sonic ikoreshwa nkabatwara ibiyobyabwenge nabashakashatsi, kandi kongeramo imiraba ya ultrasonic irashobora gutuma gaze nkeya mukigenda cya liposome-sonic, kugirango ibiyobyabwenge bisohore vuba. Nanofibers ya electrospun yakoreshejwe nabashakashatsi bo muri TPPS na ChroB mugushushanya icyitegererezo cyimiterere ine, kandi irekurwa rya pulse rishobora kugerwaho mubigana mubidukikije vivo irimo 500μg / ml protease, 50mM aside hydrochloric, pH8.6.