1. Zofunikira za HPMC
Hypromellose, dzina lonse hydroxypropyl methylcellulose, alias HPMC.Mapangidwe ake a maselo ndi C8H15O8-(C10Hl8O6)n-C8Hl5O8, ndipo kulemera kwake kwa maselo ndi pafupifupi 86000. Mankhwalawa ndi a semi-synthetic material, omwe ali mbali ya methyl ndi gawo la polyhydroxypropyl ether ya cellulose.Ikhoza kupangidwa ndi njira ziwiri: imodzi ndi yakuti kalasi yoyenera ya methyl cellulose imathandizidwa ndi NaOH, kenako imachitidwa ndi propylene oxide pansi pa kutentha kwakukulu ndi kupanikizika.Mawonekedwewa amalumikizidwa ndi mphete ya anhydroglucose ya cellulose, ndipo imatha kufika pamlingo woyenera;china ndi kuchitira thonje linter kapena nkhuni zamkati CHIKWANGWANI ndi caustic koloko, ndi kuchita ndi methyl kolorayidi ndi propylene okusayidi motsatizana kupeza izo, ndiyeno kuonjezera kuyenga , wosweka kuti zabwino ndi yunifolomu ufa kapena granules.HPMC ndi mitundu yosiyanasiyana ya cellulose yachilengedwe, komanso ndiyothandiza kwambiri pamankhwala, yomwe ili ndi magwero osiyanasiyana.Pakalipano, amagwiritsidwa ntchito kwambiri kunyumba ndi kunja, ndipo ndi imodzi mwazinthu zothandizira mankhwala zomwe zimagwiritsidwa ntchito kwambiri pamankhwala amkamwa.
Izi ndi zoyera mpaka zoyera zamkaka, zopanda poizoni komanso zopanda kukoma, ndipo zimakhala ngati ufa wa granular kapena fibrous womwe umayenda mosavuta.Ndiwokhazikika pansi pa kuwunikira komanso chinyezi.Imatupa m'madzi ozizira kuti ipange yankho la milky white colloidal, lomwe lili ndi kukhuthala kwina, ndipo chodabwitsa cha sol-gel interconversion chikhoza kuchitika chifukwa cha kusintha kwa kutentha kwa ndende inayake ya yankho.Amasungunuka kwambiri mu 70% mowa kapena dimethyl ketone, ndipo sangasungunuke mu mowa, chloroform kapena ethoxyethane.
Pamene pH ya hypromellose ili pakati pa 4.0 ndi 8.0, imakhala yokhazikika bwino, ndipo imatha kukhalapo bwino pamene pH ili pakati pa 3.0 ndi 11.0.Kutentha kwa 20 ° C ndi chinyezi chapafupi ndi 80%, chimasungidwa kwa masiku 10.Kuchuluka kwa chinyezi kwa HPMC ndi 6.2%.
Chifukwa cha zinthu zosiyanasiyana za methoxy ndi hydroxypropyl mu kapangidwe ka hypromellose, mitundu yosiyanasiyana yazinthu idawonekera.M'malo ena, mitundu yosiyanasiyana yazinthu imakhala ndi kukhuthala kwapadera komanso kutentha kwa Thermal gelation, chifukwa chake, imakhala ndi zinthu zosiyanasiyana ndipo imatha kugwiritsidwa ntchito pazifukwa zosiyanasiyana.Ma pharmacopoeias a mayiko osiyanasiyana ali ndi malamulo osiyanasiyana ndi zowonetsera pazithunzi: European Pharmacopoeia, malinga ndi magulu osiyanasiyana a viscosities ndi madigiri osiyanasiyana olowa m'malo mwa zinthu zomwe zimagulitsidwa pamsika, zimayimiridwa ndi magiredi kuphatikiza manambala, ndipo gawo ndi mPa. ·s;ku United States Pharmacopoeia, dzina lofala Onjezani manambala 4 kumapeto kuti muwonetse zomwe zili ndi mtundu wa cholowa chilichonse cha hypromellose, monga hypromellose 2208, manambala awiri oyamba amayimira pafupifupi kuchuluka kwa methoxy, ndipo manambala awiri omaliza amayimira hydroxypropyl. Pafupifupi peresenti.
2. Njira yothetsera HPMC m'madzi
2.1 njira yamadzi otentha
Popeza hypromellose sichisungunuka m'madzi otentha, imatha kumwazikana m'madzi otentha koyambirira, kenako itakhazikika.Njira ziwiri zodziwika bwino zimafotokozedwa motere:
(1) Ikani madzi otentha ofunikira mumtsuko, ndikuwotchera mpaka 70 ° C, pang'onopang'ono onjezani mankhwalawa mogwedezeka pang'onopang'ono, poyambira, mankhwalawa amayandama pamwamba pa madzi, kenako pang'onopang'ono amapanga slurry, oyambitsa Kuziziritsa slurry pansi.
(2) Onjezani 1/3 kapena 2/3 ya kuchuluka kwa madzi ofunikira mumtsuko ndikuwotcha mpaka 70 ° C kuti mumwaze mankhwalawo kuti mukonzekere slurry yamadzi otentha, kenaka yikani madzi otsalawo kapena madzi oundana mpaka madzi otentha silts Mu slurry, chisakanizocho chakhazikika pambuyo poyambitsa.
2.2 Njira yosakaniza ufa
The particles ufa ndi omwazika kwathunthu ndi youma kusanganikirana ndi wofanana kapena wokulirapo kuchuluka kwa zinthu zina powdery, ndiyeno kusungunuka m'madzi.Panthawi imeneyi, hypromellose imatha kusungunuka popanda kuphatikiza.
3. Ubwino wa HPMC
3.1 Kusungunuka kwamadzi ozizira
Kusungunuka m'madzi ozizira pansi pa 40 ° C kapena 70% ethanol, makamaka osasungunuka m'madzi otentha pamwamba pa 60 ° C, koma akhoza kusungunuka.
3.2 Kusakhazikika kwa Chemical
Hypromellose (HPMC) ndi mtundu wa ether wopanda ionic cellulose.Yankho lake lilibe mtengo wa ionic ndipo silimalumikizana ndi mchere wachitsulo kapena ma ionic organic compounds.Choncho, ena excipients sachita nawo pa kukonzekera ndondomeko.
3.3 Kukhazikika
Ndiwokhazikika ku asidi ndi zamchere, ndipo akhoza kusungidwa kwa nthawi yaitali pakati pa pH 3 ndi 1l popanda kusintha koonekeratu mu viscosity.The aqueous solution of hypromellose (HPMC) imakhala ndi anti-mildew effect ndipo imatha kusunga kukhazikika kwa mamasukidwe abwino pakasungidwe kwa nthawi yayitali.Mankhwala omwe amagwiritsa ntchito HPMC monga zowonjezera amakhala ndi kukhazikika kwabwinoko kuposa omwe amagwiritsa ntchito zopangira zachikhalidwe (monga dextrin, starch, etc.).
3.4 Kusinthika kwa viscosity
Osiyana mamasukidwe akayendedwe zotumphukira za HPMC akhoza kusakaniza malinga ndi ma ratios osiyanasiyana, ndi mamasukidwe akayendedwe ake akhoza kusintha malinga ndi malamulo ena, ndipo ali ndi ubale wabwino liniya, kotero chiŵerengero akhoza kusankhidwa malinga ndi zofunika.
3.5 Metabolic inertia
HPMC si odzipereka kapena zimapukusidwa mu thupi, ndipo sapereka kutentha, choncho ndi otetezeka mankhwala kukonzekera excipient.
3.6 Chitetezo
Nthawi zambiri amakhulupirira kuti HPMC ndi zinthu zopanda poizoni komanso zosakwiyitsa.Mlingo wakupha wapakati wa mbewa ndi 5g/kg, ndipo mlingo wapakati wakupha makoswe ndi 5.2g/kg.Mlingo watsiku ndi tsiku ndi wopanda vuto kwa anthu.
4. Kugwiritsa ntchito HPMC pokonzekera
4.1 Monga zinthu zokutira filimu ndi zinthu zopangira mafilimu
Kugwiritsa ntchito hypromellose (HPMC) ngati piritsi lophimbidwa ndi filimu, poyerekeza ndi mapiritsi ophimbidwa achikhalidwe monga mapiritsi okhala ndi shuga, mapiritsi okhala ndi shuga alibe zabwino zodziwikiratu pakubisa kukoma kwamankhwala ndi mawonekedwe, koma kuuma kwawo ndi kukhazikika kwawo, kuyamwa kwa chinyezi, kupasuka, ❖ kuyanika kulemera ndi zizindikiro zina khalidwe bwino.Gulu lochepa la viscosity la mankhwalawa limagwiritsidwa ntchito ngati filimu yosungunuka yamadzi yosungunuka pamapiritsi ndi mapiritsi, ndipo gulu lapamwamba la viscosity limagwiritsidwa ntchito ngati filimu yopangira mafilimu opangira organic zosungunulira.Nthawi zambiri zimakhala 2.0% mpaka 20%.
4.2 Monga chomangira komanso chosokoneza
Kalasi yotsika kwambiri ya mankhwalawa imatha kugwiritsidwa ntchito ngati chomangira komanso chosokoneza pamapiritsi, mapiritsi, ndi ma granules, ndipo kalasi yapamwamba kwambiri ingagwiritsidwe ntchito ngati chomangira.Mlingo umasiyanasiyana ndi mitundu yosiyanasiyana ndi zofunika.Nthawi zambiri, mlingo wa binder pamapiritsi owuma a granulation ndi 5%, ndipo mlingo wa binder pamapiritsi a granulation wonyowa ndi 2%.
4.3 Monga woyimitsa ntchito
Kuyimitsa wothandizila ndi viscous gel osakaniza mankhwala ndi hydrophilicity, amene akhoza kuchepetsa sedimentation liwiro la particles pamene ntchito suspending wothandizila, ndipo akhoza Ufumuyo pamwamba pa particles kuteteza particles kuti aggregating ndi kuchepa mu mpira. .Oyimitsa ntchito amagwira ntchito yofunika kwambiri poyimitsa.HPMC ndi zabwino kwambiri zosiyanasiyana suspending wothandizira, ndi kusungunuka colloidal njira akhoza kuchepetsa mavuto a madzi olimba mawonekedwe ndi mphamvu yaulere pa tinthu tating'ono olimba, potero utithandize bata la sakanikira kubalalitsidwa dongosolo.The mkulu-makamaka mamasukidwe kalasi kalasi ya mankhwala ntchito ngati kuyimitsidwa-mtundu wa madzi kukonzekera kukonzekera monga suspending wothandizira.Zili ndi ubwino woyimitsa, ndizosavuta kufalitsanso, sizimamatira pakhoma, ndipo zimakhala ndi particles zabwino.Mlingo wamba ndi 0.5% mpaka 1.5%.
4.4 Monga blocker, wothandizira-kutulutsa kosatha komanso woyambitsa pore
Mlingo wapamwamba kwambiri wa mankhwalawa umagwiritsidwa ntchito pokonzekera mapiritsi otulutsidwa a hydrophilic gel matrix, otsekereza ndi othandizira otulutsa omwe amapangidwa kuti azitha kutulutsa mapiritsi osakanikirana a matrix, ndipo amakhala ndi zotsatira zochedwetsa kutulutsidwa kwa mankhwala.Kugwiritsa ntchito kwake ndi 10% ~ 80% (W / W).Makalasi otsika-kukhuthala amagwiritsidwa ntchito ngati pore-forming agents pokonzekera kumasulidwa kosalekeza kapena kumasulidwa kolamuliridwa.Koyamba mlingo chofunika achire zotsatira za mtundu wa piritsi chingapezeke mwamsanga, ndiyeno kupitiriza-kumasulidwa kapena ankalamulira kumasulidwa tingati, ndi ogwira magazi mankhwala ndende anakhalabe mu thupi .Hypromellose ikakumana ndi madzi, imalowa m'madzi kuti ikhale wosanjikiza wa gel.Njira yotulutsa mankhwala kuchokera papiritsi ya matrix makamaka imaphatikizapo kufalikira kwa gel osanjikiza ndi kukokoloka kwa gel osanjikiza.
4.5 Zomatira zodzitchinjiriza monga thickener ndi colloid
Izi zikagwiritsidwa ntchito ngati thickener, ndende yomwe imagwiritsidwa ntchito kwambiri ndi 0.45% ~ 1.0%.Izi mankhwala akhoza kuonjezera bata wa guluu hydrophobic, kupanga colloid zoteteza, kuteteza particles kuchokera agglomerating ndi agglomerating, potero inhibiting mapangidwe matope, ndi ndende yake mwachizolowezi ndi 0,5% ~ 1.5%.
4.6 Kapisozi zakuthupi za makapisozi
Nthawi zambiri kapisozi chipolopolo kapisozi zakuthupi kapisozi zachokera gelatin.Kapangidwe ka chipolopolo cha kapisozi cha gelatin ndi chosavuta, koma pali zovuta ndi zochitika zina monga chitetezo chochepa ku chinyezi ndi mankhwala okhudzidwa ndi okosijeni, kutsika kwa mankhwala osokoneza bongo, komanso kuchedwa kutha kwa chipolopolo cha kapisozi panthawi yosungira.Choncho, hypromellose, monga m'malo mwa makapisozi a gelatin, amagwiritsidwa ntchito pokonzekera makapisozi, omwe amapangitsa kuti makapisozi apangidwe bwino komanso azigwiritsa ntchito makapisozi, ndipo amalimbikitsidwa kwambiri kunyumba ndi kunja.
4.7 ngati bioadhesive
Ukadaulo waukadaulo wa bioadhesion, kugwiritsa ntchito ma polima okhala ndi bioadhesive polima, kudzera kumamatira ku mucosa yachilengedwe, kumawonjezera kupitiliza ndi kulimba kwa kulumikizana pakati pa kukonzekera ndi mucous membrane, kotero kuti mankhwalawa amamasulidwa pang'onopang'ono ndikumwedwa ndi mucosa kuti akwaniritse zolinga zochizira.Pakali pano chimagwiritsidwa ntchito pochiza matenda a m'mphuno, m'kamwa mucosa ndi mbali zina.Tekinoloje ya m'mimba ya bioadhesion ndi njira yatsopano yoperekera mankhwala yomwe idapangidwa zaka zaposachedwa.Sikuti prolongs okhala nthawi yokonza mankhwala mu m`mimba thirakiti, komanso bwino kukhudzana ntchito pakati pa mankhwala ndi selo nembanemba pa mayamwidwe malo, kusintha fluidity wa selo nembanemba, Kupititsa patsogolo malowedwe a mankhwala kwa m`mimba. maselo a epithelial, potero kusintha bioavailability wa mankhwala.
4.8 Ngati gel osakaniza
Monga zomatira zokonzekera khungu, gel osakaniza ali ndi mndandanda wa ubwino monga chitetezo, kukongola, kuyeretsa kosavuta, mtengo wotsika, njira yosavuta yokonzekera, komanso kugwirizana bwino ndi mankhwala.malangizo.
Nthawi yotumiza: Dec-15-2022