Amakhepsuli aqinile/amaphilisi angenalutho e-HPMC/amaphilisi emifino/i-API esebenza kahle kakhulu kanye nezithako ezizwela umswakama/isayensi yefilimu/ukulawula ukukhululwa okuqhubekayo/ubuchwepheshe bonjiniyela be-OSD….
Ukusebenza kahle kwezindleko okuvelele, ukwenziwa lula, kanye nokulawulwa kalula kwesiguli komthamo, imikhiqizo ye-oral solid solid (OSD) ihlala iyindlela yokuphatha ekhethwayo yabathuthukisi bezidakamizwa.
Ezinkampanini ezintsha ezingama-38 zama-molecule (ama-NME) agunyazwe yi-US Food and Drug Administration ngo-2019, ezingama-26 zaziyi-OSD1. Ngo-2018, imali engenayo yemakethe yemikhiqizo enophawu lwe-OSD ngokucubungula okwesibili ama-CMO emakethe yaseNyakatho Melika yayicishe ibe ngama-dollar ayizigidi eziyizinkulungwane ezingu-7.2 USD 2. Imakethe encane yokukhipha ama-molecule kulindeleke ukuthi idlule i-USD 69 billion ngo-20243. Yonke le datha iphakamisa ukuthi ngomlomo. amafomu omthamo oqinile (ama-OSD) azoqhubeka esebenza.
Amathebulethi asabusa imakethe ye-OSD, kodwa amaphilisi aqinile aba enye indlela ekhangayo. Lokhu ngokwengxenye kungenxa yokuthembeka kwama-capsules njengendlela yokuphatha, ikakhulukazi lawo anama-API anamandla e-antitumor API. Amaphilisi asondelene kakhulu neziguli, afihla iphunga elibi nokunambitha, futhi kulula ukuwagwinya, angcono kakhulu kunamanye amafomu omthamo.
UJulien Lamps, uMphathi Womkhiqizo kwaLonza Capsules kanye Nezithako Zezempilo, uxoxa ngezinzuzo ezihlukahlukene zamaphilisi aqinile phezu kwamaphilisi. Wabelana ngemininingwane yakhe ngamaphilisi angenalutho e-hydroxypropyl methylcellulose (HPMC) nokuthi angasiza kanjani abathuthukisi bezidakamizwa ukuthi bathuthukise imikhiqizo yabo ngenkathi behlangabezana nesidingo sabathengi semithi ethathwe ezitshalweni.
Amaphilisi aqinile: Thuthukisa ukuthobela kwesiguli futhi uthuthukise ukusebenza
Iziguli zivame ukulwa nemithi enambithekayo noma enuka kabi, okunzima ukuyigwinya, noma engase ibe nemiphumela emibi. Unalokhu emqondweni, ukwenza amafomu emithamo asebenziseka kalula kungathuthukisa ukuthobela kwesiguli nemithi yokwelashwa. Amaphilisi aqinile ayinketho ekhangayo ezigulini ngoba, ngaphezu kokufihla ukunambitheka nephunga, angathathwa kancane, anciphise umthwalo wethebhulethi, futhi abe nezikhathi zokukhululwa ezingcono, ngokusebenzisa ukukhishwa okusheshayo, ukukhishwa okulawulwayo nokukhululwa kancane zuza.
Ukulawulwa okungcono kokuziphatha kokukhishwa kwesidakamizwa, isibonelo nge-micropelletizing i-API, kunganqanda ukulahlwa komthamo futhi kunciphise imiphumela emibi. Abathuthukisi bezidakamizwa bathola ukuthi ukuhlanganisa ubuchwepheshe be-multiparticulate namaphilisi kukhulisa ukuguquguquka nokusebenza kahle kokucubungula okulawulwayo kokukhishwa kwe-API. Ingakwazi ngisho nokusekela ama-pellets aqukethe ama-API ahlukene ku-capsule efanayo, okusho ukuthi izidakamizwa eziningi zingasetshenziswa ngesikhathi esisodwa ngemithamo ehlukene, kuqhubeke kuncishiswe imvamisa ye-dosing.
Ukuziphatha kwe-pharmacokinetic kanye ne-pharmacodynamic yalokhu kwakheka, okuhlanganisa i-multiparticulate system4, i-extrusion spheronization API3, kanye ne-fixed-dose combination system5, nakho kubonise ukukhiqiza kabusha okungcono uma kuqhathaniswa nokwakheka okuvamile.
Kungenxa yalokhu kuthuthukiswa okungaba khona kokuthobela isiguli nokusebenza ngempumelelo okwenza isidingo semakethe sama-API ayimbudumbudu ahlanganiswe kumaphilisi aqinile siqhubeka nokukhula.
Okuncanyelwayo kwe-polymer:
Isidingo samaphilisi emifino ukuze athathele amaphilisi e-gelatin aqinile
Ama-capsules aqinile endabuko enziwe nge-gelatin, noma kunjalo, amaphilisi aqinile e-gelatin angaletha izinselele lapho ehlangabezana nokuqukethwe kwe-hygroscopic noma okuzwela umswakama. I-Gelatin iwumkhiqizo osuselwe esilwaneni othambekele ekuphenduleni okuxhumanisayo okuthinta ukuziphatha kokuhlakazeka, futhi inokuqukethwe kwamanzi okuphezulu uma kuqhathaniswa ukuze igcine ukuguquguquka kwayo, kodwa ingase futhi ishintshisane ngamanzi nama-API kanye nezinto ezisizayo.
Ngokungeziwe kumthelela wezinto zekhephuseli ekusebenzeni komkhiqizo, iziguli eziningi ziyangabaza ukudla imikhiqizo yezilwane ngenxa yezizathu zomphakathi noma zamasiko futhi zifuna imithi ethathwe esitshalweni noma ye-vegan. Ukuze kuhlangatshezwane nalesi sidingo, izinkampani ezenza imithi nazo ziyaqhubeka nokutshala izimali ezinhlotsheni ezintsha zokudosa ukuze zenze ezinye izindlela ezisekelwe esitshalweni eziphephile nezisebenzayo. Ukuthuthuka kwesayensi yezinto zokwenza ama-capsules angenalutho athathwe esitshalweni abe nokwenzeka, anikeze iziguli inketho engatholakali esilwaneni ngaphezu kwezinzuzo ze-gelatin capsules-ukugwinya, ukukhiqiza kalula, kanye nokuphumelela kwezindleko.
Ukuze kuhlakazwe kangcono nokuhambisana:
Ukusetshenziswa kwe-HPMC
Njengamanje, enye yezindlela ezingcono kakhulu zokusebenzisa i-gelatin i-hydroxypropyl methylcellulose (HPMC), i-polymer etholakala emicu yesihlahla.
I-HPMC ayisebenzi ngamakhemikhali kancane kune-gelatin futhi imunca amanzi amancane kune-gelatin6. Okuqukethwe kwamanzi aphansi kwama-capsules e-HPMC kunciphisa ukushintshaniswa kwamanzi phakathi kwe-capsule nokuqukethwe, okuthi kwezinye izimo kungathuthukisa ukuzinza kwamakhemikhali nokomzimba kokubunjwa, kunwebe impilo yeshalofu, futhi kuhlangabezane kalula nezinselele ze-hygroscopic APIs kanye ne-excipients. Amaphilisi angenalutho e-HPMC awazwani nezinga lokushisa futhi kulula ukuwagcina nokuwahambisa.
Ngokukhula kwama-API asebenza kahle kakhulu, izidingo zokwakheka ziya ngokuya ziba yinkimbinkimbi. Kuze kube manje, abathuthukisi bezidakamizwa bathole imiphumela emihle kakhulu ohlelweni lokuhlola ukusetshenziswa kwamaphilisi e-HPMC ukuze athathele amaphilisi e-gelatin endabuko. Eqinisweni, amaphilisi e-HPMC njengamanje athandwa kakhulu ezivivinyweni zomtholampilo ngenxa yokuhambisana kwawo okuhle nemithi eminingi kanye nezinto ezisizayo7.
Ukuthuthukiswa okuqhubekayo kubuchwepheshe be-capsule ye-HPMC kuphinde kusho ukuthi abathuthukisi bezidakamizwa bangakwazi kangcono ukusebenzisa amapharamitha ayo okuhlakazeka kanye nokuhambisana nebanga elibanzi lama-NME, okuhlanganisa izinhlanganisela ezinamandla kakhulu.
Amaphilisi e-HPMC angenayo i-ejenti ye-gelling anezakhiwo ezinhle kakhulu zokuncibilika ngaphandle kokuncika kwe-ion ne-pH, ukuze iziguli zithole umphumela ofanayo wokwelapha lapho zithatha umuthi esiswini esingenalutho noma ngokudla. Njengoba kuboniswe kuMfanekiso 1.8
Ngenxa yalokho, ukuthuthukiswa kokuqedwa kungase kuvumele iziguli ukuthi zingabi nokungabaza mayelana nokuhlela imithamo yazo, ngaleyo ndlela kwandise ukuthobela.
Ukwengeza, ukuthuthukiswa okuqhubekayo kwezixazululo ze-membrane ye-capsule ye-HPMC kungenza futhi ukuvikelwa kwamathumbu nokukhululwa ngokushesha ezindaweni ezithile zomgudu wokugaya ukudla, ukulethwa kwezidakamizwa okuhlosiwe kwezinye izindlela zokwelapha, futhi kuthuthukise nakakhulu ukusetshenziswa okungahle kube khona kwama-capsules e-HPMC.
Enye indlela yokusetshenziswa kwamaphilisi e-HPMC kusemishinini yokuhogela yokulawulwa kwamaphaphu. Isidingo semakethe siyaqhubeka sikhula ngenxa ye-bioavailability ethuthukisiwe ngokugwema umphumela we-hepatic first pass kanye nokuhlinzeka ngomzila oqondile wokulawula lapho kubhekiswe ezifweni ezinjengesifuba somoya kanye nesifo esingamahlalakhona sokuvimbela amaphaphu (COPD) ngale ndlela yokulawula .
Abakhiqizi bezidakamizwa bahlale bebheke ukuthuthukisa izindlela zokwelapha ezingabizi kakhulu, ezilungele isiguli, futhi ezisebenzayo zezifo zokuphefumula, kanye nokuhlola izindlela zokwelapha ezihogeliwe zokulethwa kwezidakamizwa kwezinye izifo zesistimu yezinzwa (CNS). isidingo siyanda.
Okuqukethwe kwamanzi okuphansi kwamakhepsuli e-HPMC kuwenza alungele ama-API angezwani ne-hygroscopic noma angezwani namanzi, nakuba izakhiwo ze-electrostatic phakathi kokwakhiwa namakhepsuli angenalutho kufanele zicatshangelwe phakathi nokuthuthukiswa8.
imicabango yokugcina
Ukuthuthukiswa kwesayensi ye-membrane kanye nobuchwepheshe bonjiniyela be-OSD kuye kwabeka isisekelo sokuthi amaphilisi e-HPMC athathe indawo yamakhepsuli e-gelatin kwezinye izinhlobo, okuhlinzeka ngezinketho eziningi zokuthuthukisa ukusebenza komkhiqizo. Ngaphezu kwalokho, ukugcizelela okwandayo kokuthandwa ngabathengi kanye nesidingo esikhulayo semithi eshibhile ehogelwe kukhulise isidingo samaphilisi angenalutho ahambisana kangcono nama-molecule azwela umswakama.
Kodwa-ke, ukukhethwa kwezinto ezibonakalayo ze-membrane kuyisihluthulelo sokuqinisekisa impumelelo yomkhiqizo, futhi ukukhetha okufanele phakathi kwe-gelatin ne-HPMC kungenziwa kuphela ngobuchwepheshe obufanele. Ukukhetha okulungile kwe-membrane okubalulekile akukwazi nje ukuthuthukisa ukusebenza kahle nokunciphisa ukusabela okubi, kodwa futhi kusiza ukunqoba izinselele ezithile zokwakheka.
Isikhathi sokuthumela: Sep-23-2022