Abubuwan da aka Ci gaba da Sakin Pharmaceutical

01 Cellulose ether

Ana iya raba cellulose zuwa guda ethers da gauraye ethers bisa ga nau'in maye gurbin. Akwai nau'i ɗaya kawai na maye gurbin a cikin ether guda ɗaya, irin su methyl cellulose (MC), ethyl cellulose (EC), hydroxyl Propyl cellulose (HPC), da dai sauransu; za a iya samun madogara biyu ko fiye a cikin ether mai gauraye, wanda aka fi amfani da shi shine hydroxypropyl methyl cellulose (HPMC), ethyl methyl cellulose (EMC), da dai sauransu. Abubuwan da ake amfani da su a cikin shirye-shiryen magungunan bugun bugun jini ana wakilta ta gauraya ether HPMC, guda ether HPC, da EC, waɗanda galibi ana amfani da su azaman masu tarwatsawa, masu kumburi, retarders, da kayan shafa na fim.

1.1 Hydroxypropylmethylcellulose (HPMC)

Saboda daban-daban digiri na maye gurbin methoxy da hydroxypropyl kungiyoyin, HPMC gaba ɗaya ya kasu kashi uku a kasashen waje: K, E da F. Daga cikin su, K jerin yana da mafi sauri hydration gudun kuma ya dace a matsayin kwarangwal abu don dorewa da sarrafawa. shirye-shiryen saki. Hakanan wakili ne na sakin bugun jini. Ɗaya daga cikin masu ɗaukar magunguna da aka fi amfani da su a cikin shirye-shiryen magunguna. HPMC shine ether mai narkewa wanda ba na ionic cellulose ba, farin foda, mara daɗi, mara wari kuma mara guba, kuma ana fitar dashi ba tare da wani canji a jikin ɗan adam ba. Ba a iya narkewa a cikin ruwan zafi sama da 60°C kuma yana iya kumbura kawai; lokacin da abubuwan da suka samo asali tare da viscosities daban-daban suna haɗuwa a cikin nau'i daban-daban, haɗin kai yana da kyau, kuma gel ɗin da aka kafa zai iya sarrafa yaduwar ruwa da kuma sakin miyagun ƙwayoyi.

HPMC ɗaya ne daga cikin kayan polymer ɗin da aka saba amfani da su dangane da kumburi ko yazawar ƙwayar cuta mai sarrafa ƙwayar cuta a cikin tsarin sakin bugun jini. Kumburi miyagun ƙwayoyi saki ne don shirya aiki Pharmaceutical sinadaran a cikin Allunan ko pellets, sa'an nan Multi-Layer shafi, da m Layer ne Ruwa-insoluble amma ruwa-permeable polymer shafi, ciki Layer ne polymer tare da kumburi ikon, a lõkacin da ruwa shiga cikin. Layer na ciki, kumburi zai haifar da matsa lamba, kuma bayan wani lokaci, miyagun ƙwayoyi za su kumbura kuma a sarrafa su don saki miyagun ƙwayoyi; yayin da maganin sakin yazawa ya kasance ta hanyar ainihin kunshin magunguna. Rufewa tare da polymers mai lalacewa ko ruwa, daidaita kauri don sarrafa lokacin sakin miyagun ƙwayoyi.

Wasu masu bincike sun binciki sakin da haɓaka halaye na allunan bisa ga HPMC hydrophilic, kuma sun gano cewa adadin sakin shine sau 5 a hankali fiye da na allunan talakawa kuma yana da haɓaka babba.

Har yanzu suna da mai bincike don amfani da pseudoephedrine hydrochloride azaman magani na samfurin, hanyar ɗaukar busassun shafi, shirya gashi Layer tare da HPMC daban-daban viscosities, daidaita sakin magani. Sakamakon gwaje-gwajen in vivo ya nuna cewa a ƙarƙashin irin wannan kauri, ƙananan danko na HPMC zai iya kaiwa ga mafi girma a cikin 5h, yayin da high-viscosity HPMC ya kai matsayi mafi girma a cikin kimanin 10h. Wannan yana nuna cewa lokacin da aka yi amfani da HPMC azaman kayan shafa, dankon sa yana da tasiri mai mahimmanci akan halayen sakin ƙwayoyi.

Masu binciken sun yi amfani da verapamil hydrochloride a matsayin samfurin samfurin don shirya allunan ƙwanƙwasa nau'in nau'in nau'in nau'in nau'in nau'in nau'in nau'in nau'in nau'in nau'in nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i nau'i na HPMC K4M (15%, 20%, 25%, 30%, 35%, w / w; 4M). Yana nufin tasirin danko (4000 centipoise) a kan lokaci mai tsawo An ƙaddara abun ciki don zama 25% Wannan yana nuna cewa HPMC na iya jinkirta fitowar ainihin maganin ta hanyar hana magani daga haɗuwa da ruwa kuma yana taka rawa wajen saki mai sarrafawa.

1.2 Hydroxypropylcellulose (HPC)

Ana iya raba HPC zuwa ƙananan musanya hydroxypropyl cellulose (L-HPC) da babban maye gurbin hydroxypropyl cellulose (H-HPC). L-HPC ba ionic ba ne, fari ko fari-farin foda, mara wari kuma maras ɗanɗano, kuma matsakaici ne mara lahani na cellulose wanda ba shi da lahani ga jikin ɗan adam. Saboda L-HPC yana da babban fili da porosity, yana iya saurin sha ruwa ya kumbura, kuma adadin faɗaɗawar ruwa shine 500-700%. Shiga cikin jini, don haka zai iya inganta sakin miyagun ƙwayoyi a cikin kwamfutar hannu mai yawa da kuma pellet core, kuma yana inganta tasirin warkewa sosai.

A cikin allunan ko pellets, ƙara L-HPC yana taimaka wa kwamfutar hannu core (ko pellet core) don faɗaɗa don samar da ƙarfi na ciki, wanda ke karya Layer Layer kuma ya saki miyagun ƙwayoyi a cikin bugun jini. Masu binciken sun yi amfani da sulpiride hydrochloride, metoclopramide hydrochloride, diclofenac sodium, da nilvadipine a matsayin magungunan samfurin, da ƙananan maye gurbin hydroxypropyl cellulose (L-HPC) a matsayin wakili mai tarwatsewa. Gwaje-gwajen sun nuna cewa kauri daga cikin kumburin Layer yana ƙayyade girman barbashi. zaman banza.

Masu binciken sun yi amfani da magungunan antihypertensive a matsayin abin binciken. A cikin gwajin, L-HPC ya kasance a cikin allunan da capsules, don su sha ruwa sannan su bace don sakin maganin da sauri.

Masu binciken sun yi amfani da pellets na sulfate na terbutaline a matsayin samfurin samfurin, kuma sakamakon gwajin farko ya nuna cewa yin amfani da L-HPC a matsayin kayan da ke cikin rufin ciki da kuma ƙara SDS da ya dace a cikin launi na ciki zai iya cimma sakamakon da ake tsammanin bugun jini.

1.3 Ethyl cellulose (EC) da kuma ruwa watsawa (ECD)

EC ne maras ionic, ruwa-insoluble cellulose alkyl ether, wanda yana da halaye na sinadaran juriya, gishiri juriya, alkali juriya da zafi kwanciyar hankali, kuma yana da fadi da kewayon danko (kwayoyin halitta nauyi) da kuma kyau tufafi yi , iya samar da wani shafi Layer tare da mai kyau tauri kuma ba sauki sa, wanda ya sa shi yadu amfani a cikin miyagun ƙwayoyi ci da sarrafa saki fim shafi.

ECD wani tsari ne mai ban sha'awa wanda aka dakatar da ethyl cellulose a cikin ruwa mai rarraba (ruwa) a cikin nau'i na ƙananan ƙwayoyin colloidal kuma yana da kwanciyar hankali na jiki. Ana amfani da polymer mai narkewar ruwa wanda ke aiki azaman wakili mai haifar da pore don daidaita ƙimar sakin ECD don biyan buƙatun ci gaba da sakin magunguna don shirye-shiryen ci gaba.

EC abu ne mai mahimmanci don shirye-shiryen capsules marasa narkewa. Masu bincike sun yi amfani da dichloromethane / cikakkar ethanol / ethyl acetate (4 / 0.8 / 0.2) a matsayin mai narkewa da EC (45cp) don shirya 11.5% (w / v) EC bayani, shirya EC capsule jiki, da kuma shirya EC capsule maras permeable. saduwa da buƙatun sakin bugun bugun baki. Masu binciken sunyi amfani da theophylline a matsayin samfurin samfurin don nazarin ci gaban tsarin bugun jini mai yawa wanda aka rufe da ethyl cellulose aqueous watsawa. Sakamakon ya nuna cewa nau'in Aquacoat® a cikin ECD yana da rauni kuma yana da sauƙin karya, yana tabbatar da cewa za'a iya fitar da maganin a cikin bugun jini.

Bugu da kari, masu binciken sun yi nazari kan nau'in nau'in saki mai sarrafa bugun jini da aka shirya tare da tarwatsewar ruwa na ethyl cellulose a matsayin Layer na waje. Lokacin da nauyin nauyin rufin rufin waje ya kasance 13%, an sami nasarar sakin miyagun ƙwayoyi tare da lokaci mai tsawo na 5 h da kuma lokaci na 1.5 h. Fiye da 80% na tasirin sakin bugun jini.

02 Acrylic resin

Acrylic resin wani nau'i ne na fili na polymer da aka samar ta hanyar copolymerization na acrylic acid da methacrylic acid ko esters su a wani yanki. Resin acrylic da aka saba amfani da shi shine Eudragit azaman sunan kasuwancin sa, wanda ke da kyawawan kaddarorin shirya fina-finai kuma yana da nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan iri iri iri ne, mai narkewa mai narkewar E, nau'in L, S, da RL da RS wanda ba zai iya narkewa ba. Saboda Eudragit yana da abũbuwan amfãni daga m film-forming yi da kuma mai kyau karfinsu a tsakanin daban-daban model, shi da aka yadu amfani da fim shafi, matrix shirye-shirye, microspheres da sauran bugun jini saki tsarin.

Masu binciken sun yi amfani da nitrendipine a matsayin samfurin samfurin da Eudragit E-100 a matsayin muhimmin abu mai mahimmanci don shirya pH-m pellets, da kuma kimanta su bioavailability a cikin lafiya karnuka. Sakamakon binciken ya gano cewa tsarin mai girma uku na Eudragit E-100 yana ba da damar fitar da shi cikin sauri cikin mintuna 30 a ƙarƙashin yanayin acidic. Lokacin da pellets suke a pH 1.2, lokacin jinkirin shine 2 hours, a pH 6.4, lokacin lag shine 2 hours, kuma a pH 7.8, lokacin lag shine sa'o'i 3, wanda zai iya gane sarrafawar sakin sarrafawa a cikin fili na hanji.

Masu binciken sun gudanar da adadin 9: 1, 8: 2, 7: 3 da 6: 4 akan kayan aikin fim Eudragit RS da Eudragit RL bi da bi, kuma sun gano cewa lokacin ya kasance 10h lokacin da rabon ya kasance 9: 1. , kuma lokacin ya kasance 10h lokacin da rabo ya kasance 8: 2. Lokacin jinkirin shine 7h da 2, lokacin jinkiri a 7: 3 shine 5h, kuma lokacin da aka jinkirta a 6: 4 shine 2h; don porogens Eudragit L100 da Eudragit S100, Eudragit L100 na iya cimma manufar bugun jini na 5h lag a cikin yanayin pH5-7; 20%. Sharuɗɗan da ke sama zasu iya cimma manufar rashin lokaci na 5.1 h a pH 6.5 da lokacin sakin bugun jini na 3 hours.

03 Polyvinylpyrrolidones (PVP)

PVP wani fili ne mai narkewar ruwa wanda ba shi da ionic polymer wanda aka sanya shi daga N-vinylpyrrolidone (NVP). An raba shi zuwa maki hudu bisa ga matsakaicin nauyin kwayoyin halitta. Yawanci ana bayyana shi ta ƙimar K. Mafi girman danko, da karfi da mannewa. PVP gel (foda) yana da tasiri mai karfi akan yawancin kwayoyi. Bayan shiga ciki ko jini, saboda tsananin kumburin dukiyarsa, ana sakin maganin a hankali. Ana iya amfani da shi azaman ingantaccen wakili mai dorewa a cikin PDDS.

Vereapamil Pugse Osmotic PLOT Ormp na Layer-Layer, Layer na ciki an yi shi da kayan masarufi, wanda ya cika ruwa, wanda ya kawo lag, kuma tura Layer yana kumbura da karfi lokacin da ya ci karo da ruwa, yana fitar da miyagun ƙwayoyi daga cikin rami na saki, kuma ma'aunin matsa lamba na osmotic shine mabuɗin nasarar tsarin.

Masu binciken sun yi amfani da allunan sarrafa-saki-verapamil hydrochloride azaman samfuran samfuri, kuma sun yi amfani da PVP S630 da PVP K90 tare da viscos daban-daban azaman kayan shafa mai sarrafawa. Lokacin da nauyin fim ɗin ya kasance 8%, lokacin lag (tlag) don isa sakin vitro shine sa'o'i 3-4, kuma matsakaicin sakin (Rt) shine 20-26 mg / h.

04 Hydrogel

4.1. Alginic acid

Alginic acid fari ne ko launin rawaya mai haske, mara wari kuma mara daɗi, cellulose na halitta wanda ba ya narkewa a cikin ruwa. Tsarin sol-gel mai laushi da kyakkyawar daidaituwa ta alginic acid sun dace da yin microcapsules waɗanda ke sakin ko haɗa magunguna, sunadarai da ƙwayoyin cuta - sabon nau'in sashi a cikin PDDS a cikin 'yan shekarun nan.

Masu binciken sunyi amfani da dextran a matsayin samfurin samfurin da kuma calcium alginate gel a matsayin mai ɗaukar magunguna don yin shiri na bugun jini. Sakamako Da miyagun ƙwayoyi tare da babban nauyin kwayoyin halitta yana nuna sakin lokaci-lag-bugu, kuma za'a iya daidaita lagwar lokacin ta hanyar kauri na fim ɗin shafa.

Masu binciken sunyi amfani da sodium alginate-chitosan don samar da microcapsules ta hanyar hulɗar electrostatic. Gwaje-gwaje sun nuna cewa microcapsules suna da kyakkyawar amsawar pH, sakin sifili a pH=12, da sakin bugun jini a pH=6.8. Za'a iya amfani da lanƙwan sakin Form S, azaman ƙirar bugun jini mai amsa pH.

4.2. Polyacrylamide (PAM) da abubuwan da suka samo asali

PAM da abubuwan da suka samo asali ne manyan polymers na kwayoyin halitta masu narkewa da ruwa, waɗanda galibi ana amfani da su a cikin tsarin sakin bugun jini. Hydrogel mai zafi mai zafi zai iya jujjuyawar haɓakawa da haɓakawa (raguwa) tare da canjin yanayin zafi na waje, yana haifar da canji a cikin haɓaka, ta haka Don cimma manufar sarrafa sakin miyagun ƙwayoyi.

Mafi yawan binciken shine N-isopropylacrylamide (NIPAAm) hydrogel, tare da mahimmancin narkewa (LCST) na 32°C. Lokacin da yawan zafin jiki ya fi LCST, gel ɗin yana raguwa, kuma mai narkewa a cikin tsarin cibiyar sadarwa yana matsewa, yana sakin babban adadin maganin ruwa mai ɗauke da Drug; lokacin da yawan zafin jiki ya kasance ƙasa da LCST, gel zai iya sake sakewa, kuma za'a iya amfani da zafin zafin jiki na NPAAm gel don daidaita yanayin kumburi, girman gel, siffar, da dai sauransu don cimma daidaitattun zafin jiki na "on-off" miyagun ƙwayoyi da kuma Adadin sakin magunguna thermosensitive hydrogel pulsatile sarrafa sakin tsari.

Masu binciken sun yi amfani da wani nau'i na hydrogel-m zafin jiki (N-isopropylacrylamide) da superferric baƙin ƙarfe tetroxide barbashi a matsayin abu. An canza tsarin cibiyar sadarwa na hydrogel, don haka yana haɓaka sakin miyagun ƙwayoyi da samun tasirin bugun bugun jini.

05 sauran nau'ikan

Baya ga yaɗuwar amfani da kayan polymer na gargajiya irin su HPMC, CMS-Na, PVP, Eudragit, da Surlease, sauran sabbin kayan jigilar kayayyaki kamar haske, wutar lantarki, filayen maganadisu, raƙuman ruwa na ultrasonic, da nanofibers an ci gaba da haɓaka su. Misali, ana amfani da liposome na sonic-sensitive a matsayin mai ɗaukar magunguna ta masu bincike, kuma ƙari na raƙuman ruwa na ultrasonic na iya yin ɗan ƙaramin iskar gas a cikin motsin liposome mai saurin sonic, ta yadda za a iya fitar da maganin cikin sauri. Masu bincike a cikin TPPS da ChroB sun yi amfani da electrospun nanofibers don tsara tsarin tsari mai Layer huɗu, kuma ana iya samun sakin bugun bugun jini a cikin simulated a cikin yanayin vivo mai ɗauke da 500.μg/ml protease, 50mM hydrochloric acid, pH8.6.