Mankhwala Osasunthika Otulutsidwa

01 Cellulose ether

Ma cellulose amatha kugawidwa kukhala ma ether amodzi ndi ma ether osakanikirana motengera mtundu wa zolowa m'malo. Pali mtundu umodzi wokha wolowa m'malo mwa ether imodzi, monga methyl cellulose (MC), ethyl cellulose (EC), hydroxyl Propyl cellulose (HPC), etc.; pakhoza kukhala zolowa ziwiri kapena zingapo mu ether yosakanikirana, yomwe imagwiritsidwa ntchito kwambiri ndi hydroxypropyl methyl cellulose (HPMC), ethyl methyl cellulose (EMC), etc. Zomwe zimagwiritsidwa ntchito pokonzekera mankhwala opangidwa ndi pulse-release zimayimiridwa ndi ether HPMC yosakanizidwa, single ether HPC, ndi EC, yomwe nthawi zambiri imagwiritsidwa ntchito ngati disintegrants, kutupa, retarders, ndi zipangizo zokutira mafilimu.

1.1 Hydroxypropylmethylcellulose (HPMC)

Chifukwa cha magawo osiyanasiyana a m'malo mwa magulu a methoxy ndi hydroxypropyl, HPMC nthawi zambiri imagawidwa m'mitundu itatu kunja: K, E ndi F. Pakati pawo, mndandanda wa K uli ndi liwiro lachangu kwambiri la hydration ndipo ndi woyenera ngati chigoba chokhazikika komanso chowongolera. kumasula kukonzekera. Ilinso ndi pulse release agent. Mmodzi mwa anthu ambiri ntchito zonyamulira mankhwala mu mankhwala kukonzekera. HPMC ndi madzi osungunuka a non-ionic cellulose ether, ufa woyera, wopanda pake, wopanda fungo komanso wopanda poizoni, ndipo amachotsedwa popanda kusintha kulikonse m'thupi la munthu. Sisungunuka m'madzi otentha kuposa 60°C ndipo akhoza kutupa; pamene zotumphukira zake zokhala ndi ma viscosities osiyanasiyana zimasakanizidwa mosiyanasiyana, ubale wa mzere ndi wabwino, ndipo gel opangidwa amatha kuwongolera bwino kufalikira kwa madzi ndi kutulutsa mankhwala.

HPMC ndi imodzi mwazinthu zomwe zimagwiritsidwa ntchito polima potengera kutupa kapena kukokoloka komwe kumayendetsedwa ndi njira yotulutsira mankhwala mu dongosolo lamanjenje. Kutupa mankhwala kumasulidwa ndi kukonzekera yogwira mankhwala zosakaniza mu mapiritsi kapena pellets, ndiyeno Mipikisano wosanjikiza ❖ kuyanika, wosanjikiza wakunja ndi Madzi-insoluble koma madzi permeable polima ❖ kuyanika, wosanjikiza wamkati ndi polima ndi kutupa mphamvu, pamene madzi amalowa mu. wosanjikiza wamkati, kutupa kudzapanga kupanikizika, ndipo pakapita nthawi, mankhwalawa adzatupa ndikuwongolera kuti amasule mankhwalawa; pamene kukokoloka kumasulidwa mankhwala kudzera pachimake mankhwala phukusi. Kupaka ndi madzi-insoluble kapena kukokoloka ma polima, kusintha makulidwe ❖ kuyanika kulamulira mankhwala kumasulidwa nthawi.

Ofufuza ena adafufuza za kutulutsidwa ndi kukulitsa kwa mapiritsi kutengera hydrophilic HPMC, ndipo adapeza kuti kutulutsa kwake kumakhala kocheperako ka 5 kuposa mapiritsi wamba ndipo kumakulitsa kwambiri.

Akadali ndi wofufuza ntchito pseudoephedrine hydrochloride monga mankhwala chitsanzo, kutengera youma ❖ kuyanika njira, kukonzekera malaya wosanjikiza ndi HPMC a viscosities osiyana, kusintha amasulidwe mankhwala. Zotsatira za kuyesa kwa vivo zikuwonetsa kuti pansi pa makulidwe omwewo, HPMC yotsika kwambiri imatha kufika pachimake mu 5h, pomwe HPMC yayikulu kwambiri idafika pachimake pafupifupi 10h. Izi zikuwonetsa kuti HPMC ikagwiritsidwa ntchito ngati zokutira, kukhuthala kwake kumakhudza kwambiri khalidwe lotulutsa mankhwala.

Ofufuzawa adagwiritsa ntchito verapamil hydrochloride ngati mankhwala achitsanzo pokonzekera mapiritsi apakati pamapiritsi atatu, ndikufufuza mitundu yosiyanasiyana ya HPMC K4M (15%, 20%, 25%, 30%, 35%, w/w; 4M. amatanthawuza zotsatira za viscosity (4000 centipoise) pa nthawi ya nthawi Zotsatira zimasonyeza kuti ndi kuwonjezeka kwa kuchuluka kwa HPMC K4M, nthawi yotsalira imayikidwa pa 4 mpaka 5 maola, kotero HPMC K4M Zomwe zili mkati zimatsimikiziridwa kukhala 25%. Izi zikuwonetsa kuti HPMC ikhoza kuchedwetsa kutulutsidwa kwa mankhwala apakati poletsa mankhwalawa kuti asakhudzidwe ndi madzi ndikuchita nawo gawo pakumasulidwa.

1.2 Hydroxypropylcellulose (HPC)

HPC ikhoza kugawidwa mu low-substituted hydroxypropyl cellulose (L-HPC) ndi high-substituted hydroxypropyl cellulose (H-HPC). L-HPC ndi ufa wosakhala wa ionic, woyera kapena woyera, wopanda fungo komanso wosakoma, ndipo ndi wapakatikati Wopanda poizoni wa cellulose wopangidwa ndi cellulose yomwe ilibe vuto kwa thupi la munthu. Chifukwa L-HPC ili ndi malo akuluakulu ndi porosity, imatha kuyamwa madzi mwamsanga ndi kutupa, ndipo kuchuluka kwake kwa madzi kumawonjezeka ndi 500-700%. Kulowa mu magazi, kotero akhoza kulimbikitsa amasulidwe mankhwala mu Mipikisano wosanjikiza piritsi ndi pellet pachimake, ndi bwino kwambiri machiritso zotsatira.

M'mapiritsi kapena ma pellets, kuwonjezera L-HPC kumathandizira pachimake cha piritsi (kapena pellet core) kuti ikule kuti ipange mphamvu yamkati, yomwe imaphwanya nsanjika yophimba ndikutulutsa mankhwalawo pamphuno. Ofufuzawo anagwiritsa ntchito sulpiride hydrochloride, metoclopramide hydrochloride, diclofenac sodium, ndi nilvadipine monga mankhwala achitsanzo, ndi otsika-substituted hydroxypropyl cellulose (L-HPC) monga wothandizira kusweka. The zoyesera anasonyeza kuti makulidwe a kutupa wosanjikiza zimatsimikizira tinthu kukula. nthawi yanthawi.

Ofufuzawo adagwiritsa ntchito mankhwala a antihypertensive monga chinthu chophunzirira. Pakuyesa, L-HPC inalipo m'mapiritsi ndi makapisozi, kotero kuti amamwa madzi ndiyeno amawononga kuti amasule mankhwalawa mwamsanga.

Ofufuzawo adagwiritsa ntchito terbutaline sulfate pellets ngati mankhwala achitsanzo, ndipo zotsatira zoyamba zoyesa zidawonetsa kuti kugwiritsa ntchito L-HPC ngati chinthu chamkati chamkati ndikuwonjezera SDS yoyenera kuchipinda chamkati chamkati chingathe kukwaniritsa kutulutsidwa kwa pulse.

1.3 Ethyl cellulose (EC) ndi kupezeka kwake kwamadzi (ECD)

EC ndi non-ionic, madzi-insoluble mapadi alkyl ether, amene ali ndi makhalidwe kukana mankhwala, kukana mchere, alkali kukana ndi kutentha bata, ndipo ali osiyanasiyana mamasukidwe akayendedwe (mamolekyu kulemera) ndi ntchito bwino zovala, akhoza kupanga ❖ kuyanika wosanjikiza ndi kulimba kwabwino ndipo sikophweka kuvala, zomwe zimapangitsa kuti zigwiritsidwe ntchito kwambiri muzopaka filimu zokhazikika komanso zoyendetsedwa bwino.

ECD ndi heterogeneous system yomwe ethyl cellulose imayimitsidwa mu dispersant (madzi) mu mawonekedwe a tinthu tating'onoting'ono ta colloidal ndipo imakhala ndi kukhazikika kwathupi. Polima yosungunuka m'madzi yomwe imagwira ntchito ngati pore-forming agent imagwiritsidwa ntchito posintha kuchuluka kwa ECD kuti ikwaniritse zofunikira pakutulutsidwa kwamankhwala kosalekeza pokonzekera kumasulidwa kosalekeza.

EC ndi chinthu chabwino pokonzekera makapisozi osasungunuka m'madzi. Ofufuzawa adagwiritsa ntchito dichloromethane / absolute ethanol / ethyl acetate (4 / 0.8 / 0.2) monga zosungunulira ndi EC (45cp) kukonzekera 11.5% (w / v) EC yankho , kukonzekera thupi la EC kapisozi, ndikukonzekera kapisozi wa EC wopanda permeable kukwaniritsa zofunikira za kugunda kwapakamwa. Ofufuzawa adagwiritsa ntchito theophylline ngati mankhwala achitsanzo kuti aphunzire za chitukuko cha multiphase pulse system yokutidwa ndi ethyl cellulose amadzimadzi dispersion. Zotsatira zinawonetsa kuti mitundu ya Aquacoat® mu ECD inali yosalimba komanso yosavuta kusweka, kuwonetsetsa kuti mankhwalawa amatha kutulutsidwa mu pulse.

Kuphatikiza apo, ofufuzawo adasanthula ma pellets omasulidwa oyendetsedwa ndi pulse okonzedwa ndi ethyl cellulose amadzimadzi amwazikana ngati wosanjikiza wokutira wakunja. Pamene kulemera kwa nsanjika yakunja kunali 13%, kutulutsidwa kwa mankhwala owonjezereka kunatheka ndi nthawi ya 5 h ndi nthawi ya 1.5 h. Zoposa 80% za kutulutsa kwamphamvu.

02 Acrylic resin

Acrylic resin ndi mtundu wa polima pawiri wopangidwa ndi copolymerization wa acrylic acid ndi methacrylic acid kapena esters awo mu gawo linalake. Utoto wa acrylic womwe umagwiritsidwa ntchito kwambiri ndi Eudragit monga dzina lake lamalonda, lomwe lili ndi zinthu zabwino zopangira mafilimu ndipo lili ndi mitundu yosiyanasiyana monga chapamimba chosungunuka E mtundu, enteric-soluble L, S mtundu, ndi madzi osasungunuka RL ndi RS. Chifukwa Eudragit ali ndi ubwino wochita bwino kwambiri popanga mafilimu komanso kugwirizanitsa bwino pakati pa zitsanzo zosiyanasiyana, amagwiritsidwa ntchito kwambiri popaka mafilimu, kukonzekera matrix, ma microspheres ndi machitidwe ena otulutsa mpweya.

Ofufuzawo adagwiritsa ntchito nitrendipine ngati mankhwala achitsanzo komanso Eudragit E-100 ngati chothandizira chofunikira pokonzekera ma pellets omvera pH, ndikuwunika kupezeka kwawo mwa agalu athanzi. Zotsatira za kafukufukuyu zidapeza kuti mawonekedwe atatu a Eudragit E-100 amathandizira kuti amasulidwe mwachangu mkati mwa mphindi 30 pansi pa acidic. Pamene ma pellets ali pa pH 1.2, nthawi yotsalira ndi maola awiri, pH 6.4, nthawi yotsalira ndi maola awiri, ndipo pa pH 7.8, nthawi yotsalira ndi maola atatu, omwe amatha kuzindikira kayendetsedwe kake kakutulutsidwa m'matumbo.

Ofufuzawo adachita zowerengera za 9: 1, 8: 2, 7: 3 ndi 6: 4 pazinthu zopanga filimu Eudragit RS ndi Eudragit RL motsatana, ndipo adapeza kuti nthawi yayitali inali 10h pomwe chiŵerengero chinali 9: 1. , ndipo kuchedwa kwa nthawi kunali 10h pamene chiŵerengero chinali 8:2. Nthawi yotsalira ndi 7h pa 2, nthawi ya 7: 3 ndi 5h, ndipo nthawi ya 6: 4 ndi 2h; kwa porogens Eudragit L100 ndi Eudragit S100, Eudragit L100 ikhoza kukwaniritsa cholinga cha 5h nthawi ya lag mu pH5-7 chilengedwe; 20%, 40% ndi 50% ya yankho ❖ kuyanika, anapeza kuti ❖ kuyanika njira munali 40% EudragitL100 akhoza kukumana ndi nthawi yanthawi chofunika; zomwe zili pamwambazi zitha kukwaniritsa cholinga cha kutsalira kwa nthawi kwa 5.1 h pa pH 6.5 ndi kutulutsa kwamphamvu kwa maola atatu.

03 Polyvinylpyrrolidones (PVP)

PVP ndi polima yosungunuka m'madzi yopanda ionic yopangidwa kuchokera ku N-vinylpyrrolidone (NVP). Amagawidwa m'magulu anayi malinga ndi kulemera kwake kwa maselo. Nthawi zambiri amawonetsedwa ndi K mtengo. Kuchuluka kwa mamasukidwe akayendedwe, kumamatira mwamphamvu. Gelisi ya PVP (ufa) imakhala ndi mphamvu yotsatsira mankhwala ambiri. Pambuyo polowa m'mimba kapena m'magazi, chifukwa cha kutupa kwake kwakukulu, mankhwalawa amamasulidwa pang'onopang'ono. Itha kugwiritsidwa ntchito ngati wothandizira wokhazikika wokhazikika mu PDDS.

Piritsi la Verapamil pulse osmotic ndi piritsi la osmotic la magawo atatu, gawo lamkati limapangidwa ndi hydrophilic polima PVP ngati gawo lokankhira, ndipo chinthu cha hydrophilic chimapanga hydrophilic gel akakumana ndi madzi, omwe amalepheretsa kutulutsidwa kwa mankhwala, amapeza nthawi, ndipo amakankhira Wosanjikiza amafufuma kwambiri akakumana ndi madzi, kukankhira mankhwala kunja kwa dzenje lotulutsa, ndipo osmotic pressure propellant ndiye chinsinsi cha kupambana kwa mapangidwewo.

Ofufuzawo adagwiritsa ntchito mapiritsi otulutsidwa a verapamil hydrochloride ngati mankhwala achitsanzo, ndipo adagwiritsa ntchito PVP S630 ndi PVP K90 yokhala ndi ma viscosity osiyanasiyana ngati zida zomangira zotulutsidwa. Pamene kulemera kwa filimuyo ndi 8%, nthawi yotsalira (lag) kuti ifike mu vitro kumasulidwa ndi maola 3-4, ndipo mlingo wotulutsidwa (Rt) ndi 20-26 mg / h.

04 Hydrogel

4.1. Alginic acid

Alginic acid ndi ufa woyera kapena wopepuka wachikasu, wopanda fungo komanso wopanda kukoma, cellulose wachilengedwe wosasungunuka m'madzi. Njira yofatsa ya sol-gel ndi biocompatibility yabwino ya alginic acid ndi yoyenera kupanga ma microcapsules omwe amamasula kapena kuyika mankhwala, mapuloteni ndi maselo - mawonekedwe atsopano a mlingo mu PDDS m'zaka zaposachedwa.

Ofufuzawa adagwiritsa ntchito dextran ngati mankhwala achitsanzo komanso gel osakaniza a calcium alginate monga chonyamulira chamankhwala kuti apange kugunda kwa mtima. Zotsatira Mankhwala okhala ndi mamolekyu olemera kwambiri amawonetsa kutulutsa kwanthawi yayitali, ndipo kuchedwa kwanthawi kumatha kusinthidwa ndi makulidwe a filimu yophimba.

Ofufuzawa adagwiritsa ntchito sodium alginate-chitosan kupanga ma microcapsules kudzera mukuchita kwa electrostatic. Zoyeserera zikuwonetsa kuti ma microcapsules ali ndi kuyankha kwa pH kwabwino, kumasulidwa kwa zero pa pH = 12, ndi kutulutsa kwamphamvu pa pH = 6.8. Fomu S yokhotakhota, itha kugwiritsidwa ntchito ngati pH-responsive pulsatile formulation.

4.2. Polyacrylamide (PAM) ndi zotumphukira zake

PAM ndi zotumphukira zake ndi ma polima apamwamba osungunuka m'madzi, omwe amagwiritsidwa ntchito kwambiri pamakina otulutsa ma pulse. Hydrogel yosamva kutentha imatha kukulitsidwa mosinthika ndikukulitsa (kuchepera) ndi kusintha kwa kutentha kwakunja, kupangitsa kusintha kwamphamvu, potero Kukwaniritsa cholinga chowongolera kutulutsidwa kwa mankhwala.

Yophunzira kwambiri ndi N-isopropylacrylamide (NIPAAm) hydrogel, yokhala ndi mfundo yosungunuka kwambiri (LCST) ya 32°C. Pamene kutentha kuli kwakukulu kuposa LCST, gel osakaniza amachepa, ndi zosungunulira mu dongosolo la maukonde amafinyidwa, kutulutsa kuchuluka kwa Mankhwala okhala ndi njira yamadzimadzi; pamene kutentha kuli kotsika kuposa LCST, gel osakaniza amatha kutupa, ndipo kutentha kwa gel osakaniza NPAAm kungagwiritsidwe ntchito kusintha khalidwe la kutupa, kukula kwa gel, mawonekedwe, etc. Kutulutsa kwa mankhwala mlingo thermosensitive hydrogel pulsatile controlled release formulation.

Ofufuzawa adagwiritsa ntchito gulu la hydrogel (N-isopropylacrylamide) losakanikirana ndi kutentha komanso tinthu tating'onoting'ono tachitsulo totchedwa tetroxide. Mawonekedwe a netiweki a hydrogel amasinthidwa, potero amafulumizitsa kutulutsidwa kwa mankhwalawa ndikupeza zotsatira za kutulutsa kwamphamvu.

05 magulu ena

Kuphatikiza pakugwiritsa ntchito kwambiri zida zama polima monga HPMC, CMS-Na, PVP, Eudragit, ndi Surlease, zida zina zatsopano zonyamulira monga kuwala, magetsi, maginito, mafunde akupanga, ndi ma nanofibers zapangidwa mosalekeza. Mwachitsanzo, sonic-sensitive liposome imagwiritsidwa ntchito ngati chonyamulira cha mankhwala ndi ochita kafukufuku, ndipo kuwonjezera kwa mafunde akupanga mafunde angapangitse mpweya wochepa mu sonic-sensitive liposome kusuntha, kotero kuti mankhwalawa akhoza kumasulidwa mwamsanga. Ma electrospun nanofibers adagwiritsidwa ntchito ndi ofufuza mu TPPS ndi ChroB kupanga mawonekedwe a magawo anayi, ndipo kutulutsa kwamphamvu kumatha kuzindikirika mumayendedwe oyeserera a vivo okhala ndi 500.μg/ml protease, 50mM hydrochloric acid, pH8.6.