The ambiri excipients m`kamwa olimba mlingo mitundu

Kukonzekera kolimba ndizomwe zimafalitsidwa kwambiri komanso zomwe zimagwiritsidwa ntchito kwambiri pamsika, ndipo nthawi zambiri zimakhala ndi zinthu ziwiri zazikulu komanso zowonjezera. Zothandizira, zomwe zimadziwikanso kuti zowonjezera, zimatanthawuza mawu omwe amagwiritsidwa ntchito pazinthu zonse zowonjezera pakukonzekera kolimba kupatula mankhwala akuluakulu. Malinga ndi mawonekedwe ndi ntchito zosiyanasiyana za othandizira, zowonjezera zokonzekera zolimba nthawi zambiri zimagawidwa kukhala: zodzaza, zomangira, zosokoneza, zothira mafuta, zowongolera zotulutsa, ndipo nthawi zina zopangira utoto ndi zokometsera zimatha kuwonjezeredwanso malinga ndi zofunikira za kukonzekera. kukonza kapena kusintha maonekedwe ndi kukoma kwa mapangidwe.
Zothandizira pakukonzekera kolimba ziyenera kukwaniritsa zofunikira pakugwiritsa ntchito mankhwala, ndikukhala ndi makhalidwe awa: ①Iyenera kukhala ndi kukhazikika kwa mankhwala ndipo isakhale ndi zotsatira za thupi ndi mankhwala ndi mankhwala aakulu; ②Siziyenera kukhudza zotsatira zachirengedwe ndi zomwe zili mu mankhwala; ③Palibe chovulaza mthupi la munthu Zowopsa, ziphe zisanu, palibe zoyipa.
1. Wodzaza (woonda)
Chifukwa cha mlingo wochepa wa mankhwala aakulu, mlingo wa mankhwala ena nthawi zina ndi ma milligrams ochepa kapena zochepa, zomwe sizikugwirizana ndi kupanga mapiritsi kapena kayendetsedwe kachipatala. Choncho, pamene mankhwala akuluakulu ali osakwana 50mg, mlingo wina wa filler, wotchedwanso diluent, uyenera kuwonjezeredwa.
Kudzaza koyenera kuyenera kukhala kwa physiologically ndi mankhwala osagwira ntchito komanso osakhudza bioavailability wa mankhwala. Zodzaza zomwe zimagwiritsidwa ntchito nthawi zambiri ndi izi: ① Wowuma, wowuma wa tirigu, wowuma wa chimanga, ndi wowuma wa mbatata, pomwe wowuma wa chimanga ndi omwe amagwiritsidwa ntchito kwambiri; khola m'chilengedwe, otsika mu hygroscopicity, koma osauka compressibility; ② Lactose, yabwino mu katundu ndi compressible, madzimadzi abwino; ③ sucrose, ali amphamvu hygroscopicity; ④ pregelatinized wowuma, wotchedwanso wowuma compressible, ali wabwino compressibility, fluidity ndi kudzikonda lubricity; ⑤ cellulose ya microcrystalline, yomwe imatchedwa MCC, imakhala ndi mphamvu zomangira komanso kupanikizika kwabwino; wotchedwa "dry binder"; ⑥Mannitol, poyerekeza ndi zodzaza pamwambapa, ndizokwera mtengo pang'ono, ndipo zimagwiritsidwa ntchito m'mapiritsi omwe amatha kutafuna, omwenso amakhala ndi kukoma kosakhwima; ⑦ Mchere wa Inorganic, makamaka calcium sulfate, calcium phosphate, calcium carbonate, ndi zina zotero, wokhala ndi mphamvu zokhazikika zakuthupi ndi mankhwala.
2. Wonyowetsa wothandizira ndi zomatira
Zonyowetsa ndi zomangira ndizowonjezera zomwe zimawonjezeredwa panthawi ya granulation. The chonyowetsa wothandizira palokha si viscous, koma madzi amene amapangitsa mamasukidwe akayendedwe a zinthu mwa kunyowetsa zinthu. Zonyowetsa zomwe zimagwiritsidwa ntchito nthawi zambiri zimaphatikizapo madzi osungunuka ndi ethanol, omwe madzi osungunula ndi chisankho choyamba.
Zomatira zimatanthawuza zida zothandizira zomwe zimadalira mamasukidwe awo kuti apereke zinthu zosawoneka bwino kapena zosakwanira bwino zokhala ndi mamasukidwe oyenera. Zomatira zomwe zimagwiritsidwa ntchito nthawi zambiri zimaphatikizapo: ① Wowuma slurry, womwe ndi imodzi mwazomatira zomwe zimagwiritsidwa ntchito kwambiri, ndizotsika mtengo, ndipo zimagwira ntchito bwino, ndipo zomwe zimagwiritsidwa ntchito nthawi zambiri ndi 8% -15%; ②Methylcellulose, yotchedwa MC, ili ndi kusungunuka kwamadzi; ③Hydroxypropylcellulose, yotchedwa HPC, ingagwiritsidwe ntchito ngati ufa wopangira mapiritsi; ④Hydroxypropylmethylcellulose, yotchedwa HPMC, zinthuzo zimasungunuka m'madzi ozizira; ⑤Carboxymethylcellulose sodium, yomwe imatchedwa CMC-Na, yoyenera mankhwala omwe ali ndi mphamvu zochepa; ⑥Ethylcellulose, yotchedwa EC, zinthuzo sizisungunuka m'madzi, koma zimasungunuka mu ethanol; ⑦ Povidone, yomwe imatchedwa PVP, zinthuzo zimakhala ndi hygroscopic, zimasungunuka m'madzi ndi ethanol; ⑧ Kuphatikiza apo, pali polyethylene glycol (yotchedwa PEG), Zida monga gelatin.
3. Wosagwirizana
Ma disintegrants amatanthauza zowonjezera zomwe zimalimbikitsa kusweka kwa mapiritsi kukhala tinthu tating'onoting'ono m'madzi am'mimba. Kupatula mapiritsi apakamwa omwe ali ndi zofunikira zapadera monga mapiritsi otulutsidwa mosalekeza, mapiritsi otulutsidwa, ndi mapiritsi omwe amatha kutafuna, zosokoneza zimafunika kuwonjezeredwa. Nthawi zambiri disintegrants ntchito ndi: ① youma wowuma, oyenera insoluble kapena pang'ono sungunuka mankhwala; ② carboxymethyl wowuma sodium, wotchedwa CMS-Na, nkhaniyi ndi mkulu-mwachangu disintegrant; ③ low-substituted hydroxypropyl cellulose, yomwe imatchedwa L -HPC, yomwe imatha kutupa mofulumira itatha kumwa madzi; ④Cross-linked methyl cellulose sodium, yotchedwa CCMC-Na; zinthu zimafufuma poyamba m'madzi ndiyeno zimasungunuka, ndipo sizisungunuka mu ethanol; Choyipa chake ndi chakuti ali ndi hygroscopicity yolimba ndipo amagwiritsidwa ntchito kwambiri popangira mapiritsi otulutsa mphamvu kapena mapiritsi otsekemera; ⑥Zophatikizika zophatikizika zimaphatikizira kusakaniza kwa sodium bicarbonate ndi citric acid, ndi citric acid, fumaric acid, ndi sodium carbonate zitha kugwiritsidwanso ntchito, Potaziyamu Carbonate ndi Potaziyamu Bicarbonate etc.
4. Mafuta
Mafuta atha kugawidwa m'magulu atatu, kuphatikiza ma glidants, anti-sticking agents, ndi mafuta opaka pang'ono. ① Glidant: ntchito yake yayikulu ndikuchepetsa kukangana pakati pa tinthu tating'onoting'ono, kuwongolera kuchuluka kwa ufa, ndikuthandizira kuchepetsa kusiyana kwa kulemera kwa piritsi; ② anti-sticking agent: ntchito yake yayikulu ndikuletsa kumamatira panthawi yoponderezedwa kwa piritsi, Pofuna kuonetsetsa kuti mapiritsi akuyenda bwino, amathanso kusintha mawonekedwe a mapiritsi; ③ chivalrous lubricant: kuchepetsa kukangana pakati pa zinthu ndi khoma la nkhungu, kuti zitsimikizire kuti piritsi psinjika ndi kukankhira zikuyenda bwino. Mafuta omwe amagwiritsidwa ntchito kwambiri (munjira yotakata) amaphatikiza ufa wa talc, magnesium stearate (MS), gel osakaniza silika, polyethylene glycols, sodium lauryl sulfate, mafuta a masamba a hydrogenated, ndi zina zambiri.
5. Kutulutsa modulator
Zowongolera zotulutsa m'mapiritsi amkamwa ndi oyenera kuwongolera kuthamanga ndi kuchuluka kwa mankhwala omasulidwa mukukonzekera kumasulidwa kwapakamwa, kuti awonetsetse kuti mankhwalawa amaperekedwa kumalo odwala pa liwiro linalake ndikusunga ndende inayake mu minofu kapena madzi amthupi. , potero Pezani kuyembekezera achire zotsatira ndi kuchepetsa poizoni ndi mavuto. Zowongolera zomwe zimagwiritsidwa ntchito nthawi zambiri zimagawika m'magulu a matrix, polima-wokutidwa pang'onopang'ono kutulutsa polima ndi thickener.
(1) Matrix-mtundu wotulutsa moduli
① Hydrophilic gel skeleton material: imafufuma ikakhala m'madzi kupanga chotchinga cha gel chotchinga kutulutsa mankhwala, omwe amagwiritsidwa ntchito kwambiri ndi methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, povidone, carbomer, alginic acid Salt, chitosan, etc.
② Chigoba chosasungunuka: Chigoba chosasungunuka chimatanthawuza ma polima apamwamba omwe sasungunuka m'madzi kapena osasungunuka m'madzi. Zomwe zimagwiritsidwa ntchito makamaka ndi ethyl cellulose, polyethylene, polyethylene yapoizoni isanu, polymethacrylic acid, ethylene-vinyl acetate copolymer, mphira wa silikoni, etc.
③ Zipangizo zamakina opangidwa ndi bioerodible: Zomwe zimagwiritsidwa ntchito nthawi zambiri zimaphatikizapo mafuta anyama, mafuta a masamba a hydrogenated, phula, mowa wa stearyl, sera ya carnauba, glyceryl monostearate, ndi zina zambiri. Zitha kuchedwetsa kusungunuka ndi kutulutsa mankhwala osungunuka m'madzi.
(2) Zosintha zotulutsidwa
① Zosasungunuka za polima: zida zomwe sizingasungunuke za mafupa monga EC.
②Enteric polima zipangizo: wamba enteric polima zipangizo makamaka monga akiliriki utomoni, L-mtundu ndi S-mtundu, hydroxypropylmethylcellulose acetate succinate (HPMCAS), mapadi acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate (HPMCP), etc. pamwamba zipangizo mu madzi a m'mimba, ndi kusungunula m'madera enieni kuchita mbali.
6. Zina zowonjezera
Kuphatikiza pa zowonjezera zomwe zimagwiritsidwa ntchito pamwambazi, zowonjezera zina nthawi zina zimawonjezeredwa kuti zikwaniritse zosowa za kayendetsedwe ka mankhwala, kupititsa patsogolo kuzindikira kwa mankhwala kapena kupititsa patsogolo kumvera. Mwachitsanzo, mitundu, zokometsera ndi zotsekemera.
①Cholozera: Cholinga chachikulu chowonjezera izi ndikuwongolera mawonekedwe a piritsi ndikupangitsa kuti ikhale yosavuta kuzindikira ndikusiyanitsa. Mitundu yomwe imagwiritsidwa ntchito nthawi zambiri iyenera kukwaniritsa zofunikira zamankhwala, ndipo kuchuluka kwake kuyenera kusapitilira 0.05%.
②Zonunkhira ndi zotsekemera: Cholinga chachikulu cha zonunkhiritsa ndi zotsekemera ndikuwongolera kukoma kwamankhwala, monga mapiritsi otafuna ndi mapiritsi osweka pakamwa. Mafuta onunkhira omwe amagwiritsidwa ntchito nthawi zambiri amaphatikizanso zinthu zina, mafuta onunkhira osiyanasiyana, etc.; Zotsekemera zomwe zimagwiritsidwa ntchito nthawi zambiri zimaphatikizapo sucrose, aspartame, etc.