I-Capsule ingenye yezinhlobo zasendulo zomthamo wezidakamizwa, ezavela eGibhithe lasendulo [1].UDe Pauli, usokhemisi eVienna, wakhuluma encwadini yakhe yezokuvakasha ngo-1730 ukuthi amaphilisi e-Oval asetshenziselwa ukuvala iphunga elibi lezidakamizwa ukunciphisa ubuhlungu beziguli [2].Eminyakeni engaphezu kweyi-100 kamuva, osokhemisi uJoseph Gerard Auguste dublanc kanye noFrancois Achille Barnabe motors bathola ilungelo lobunikazi be-gelatin capsule yokuqala emhlabeni ngo-1843 futhi ngokuqhubekayo balithuthukisa ukuze livumelane nokukhiqizwa kwezimboni [3,4];Kusukela lapho, amalungelo obunikazi amaningi kuma-capsules angenalutho asezelwe.Ngo-1931, u-Arthur Colton wenkampani i-Parke Davis waklama ngempumelelo futhi wakhiqiza okokusebenza okuzenzakalelayo kwe-capsule engenalutho futhi wakhiqiza i-capsule engenalutho yokuqala emhlabeni eyenziwe ngomshini.Kuyathakazelisa ukuthi kuze kube manje, umugqa wokukhiqiza we-capsule ongenalutho uthuthukiswe ngokuqhubekayo kuphela ngesisekelo somklamo ka-Arthur wokuthuthukisa ikhwalithi yomkhiqizo nokusebenza kahle kokukhiqiza.
Njengamanje, i-capsule yenze intuthuko enkulu futhi esheshayo emkhakheni wezokunakekelwa kwempilo kanye nekhemisi, futhi isibe enye yezindlela eziyinhloko zomthamo wamalungiselelo aqinile omlomo.Kusukela ngo-1982 kuya ku-2000, phakathi kwemithi emisha egunyazwe emhlabeni wonke, amafomu omthamo we-capsule eqinile abonisa ukuthambekela okukhuphukayo.
Umfanekiso 1 Kusukela ngo-1982, imithi emisha yamangqamuzana iye yaqhathaniswa phakathi kwamaphilisi namaphilisi
Ngokuthuthuka kokukhiqizwa kwemithi kanye nemboni ye-R & D, izinzuzo zamaphilisi ziye zaqashelwa kakhulu, ikakhulukazi kulezi zici ezilandelayo:
1. Izintandokazi zesiguli
Uma kuqhathaniswa namanye amafomu omthamo, ama-capsules aqinile angakwazi ukuvala ngokuphumelelayo iphunga elibi lezidakamizwa futhi kulula ukugwinya.Imibala eyahlukene kanye nemiklamo yokuphrinta yenza izidakamizwa zibonakale kakhudlwana, ukuze kuthuthukiswe ngempumelelo ukuthobela izidakamizwa.Ngo-1983, ucwaningo olwenziwe yiziphathimandla zaseYurophu naseMelika lubonise ukuthi phakathi kweziguli eziyi-1000 ezikhethiwe, i-54% ikhetha ama-capsules aqinile, i-29% ikhetha ama-pellets afakwe ushukela, i-13% kuphela ikhetha amaphilisi, kanti enye i-4% ayizange ikhethe ngokucacile.
2. Ukusebenza Okuphezulu Kwe-R&D
Umbiko we-tufts ka-2003 waveza ukuthi izindleko zocwaningo nokuthuthukiswa kwezidakamizwa zenyuka ngamaphesenti angama-55 kusukela ngo-1995 kuya ku-2000, futhi isilinganiso sezindleko zomhlaba wonke zocwaningo nokuthuthukiswa kwezidakamizwa sesifinyelele ezigidini ezingu-897 zamadola aseMelika.Njengoba sazi sonke, imishanguzo yangaphambili ibaliwe, isikhathi sokudla kwemakethe yemithi enelungelo lobunikazi sizoba side kakhulu, futhi inzuzo yemithi emisha yezinkampani ezithaka imithi izokhula kakhulu.Isilinganiso senani le-excipients elisetshenziswe kuma-capsules laliyi-4, eyancishiswa kakhulu uma iqhathaniswa ne-8-9 kumaphilisi;Izinto zokuhlola amaphilisi nazo zincane, futhi izindleko zokusungulwa kwendlela, ukuqinisekiswa nokuhlaziya cishe ziyingxenye yamaphilisi.Ngakho-ke, uma kuqhathaniswa namaphilisi, isikhathi sokuthuthukiswa kwama-capsules okungenani isigamu sonyaka sifushane kuneso samaphilisi.
Ngokuvamile, ama-22% ezinkampani ezintsha ezihlanganisiwe ocwaningweni nasekuthuthukisweni kwezidakamizwa zingangena ezivivinyweni zomtholampilo zesigaba I, lapho okungaphansi kuka-1/4 kungaphumelela ezivivinyweni zomtholampilo zesigaba sesi-III.Ukuhlolwa kwezinhlanganisela ezintsha kunganciphisa ngempumelelo izindleko zocwaningo lwezidakamizwa ezintsha nezikhungo zokuthuthukisa ngokushesha okukhulu.Ngakho-ke, imboni yokukhiqiza i-capsule yomhlaba wonke ithuthukise amaphilisi e-preclinical (pccaps) alungele ukuhlolwa kwamagundane ®）; Imishini yokugcwalisa eyi-Precision micro (i-xcelodose) elungele ukukhiqizwa kwamasampula e-capsule yomtholampilo ®）， Futhi amaphilisi angama-double blind blind (dbcaps) afanelekile. ngezivivinyo ezinkulu zemitholampilo ®） Kanye nohlu olugcwele lwemikhiqizo esekela Ukwehliswa kwezindleko ze-R & D kanye nokuthuthukisa ukusebenza kahle kwe-R & D.
Ngaphezu kwalokho, kunezinhlobo ezingaphezu kwezingu-9 zamaphilisi ngobukhulu obuhlukahlukene, okunikeza izinketho eziningi zokuklama umthamo wezidakamizwa.Ukuthuthukiswa kobuchwepheshe bokulungiselela kanye nemishini ehlobene nakho kwenza i-capsule ifanele izinhlanganisela eziningi ezinezakhiwo ezikhethekile, njengezinhlanganisela ezingancibiliki emanzini.Ukuhlaziywa kukhombisa ukuthi amaphesenti angama-50 wezinto ezintsha ezihlanganisiwe ezitholwe ngokuhlolwa okuphezulu kanye namakhemikhali ahlanganisiwe awancibiliki emanzini (20%) μ G / ml), womabili amaphilisi agcwele uketshezi kanye namaphilisi athambile angahlangabezana nezidingo zalokhu kulungiswa kwenhlanganisela.
3. Izindleko zokukhiqiza eziphansi
Uma kuqhathaniswa namaphilisi, indawo yokusebenzela yokukhiqiza ye-GMP yama-capsules aqinile inezinzuzo zemishini yenqubo encane, ukusetshenziswa kwendawo ephezulu, ukuhlelwa okunengqondo, izikhathi ezimbalwa zokuhlola ohlelweni lokukhiqiza, imingcele yokulawula ikhwalithi encane, ama-opharetha amancane, ingozi ephansi yokungcoliswa kwesiphambano, elula. inqubo yokulungiselela, izinqubo zokukhiqiza ezincane, izinto ezisizayo ezilula kanye nezindleko eziphansi.Ngokusho kokulinganisa kochwepheshe abagunyaziwe, izindleko eziphelele zamaphilisi aqinile ziphansi ngo-25-30% kunalezo zamaphilisi [5].
Ngokuthuthuka okunamandla kwama-capsules, ama-capsules angenalutho, njengenye yezinto ezisiza kakhulu, nawo asebenza kahle.Ngo-2007, inani eliphelele lokuthengiswa kwamaphilisi angenalutho emhlabeni lidlule izigidigidi ezingama-310, lapho ama-94% awo amaphilisi angenalutho e-gelatin, kanti amanye ama-6% avela kumaphilisi angewona asuselwa ezilwaneni, okuyizinga lokukhula konyaka le-hydroxypropyl methylcellulose (HPMC). ) amaphilisi angenalutho angaphezu kwama-25%.
Ukwenyuka okukhulu ekuthengisweni kwamaphilisi angenalutho okungezona ezilwane kukhombisa inkambiso yokusetshenziswa kokukhangisa imikhiqizo yemvelo emhlabeni.E-United States iyodwa, isibonelo, kunabantu abayizigidi ezingu-70 “abangakaze badle imikhiqizo ephuma ezilwaneni”, futhi amaphesenti angu-20 engqikithi yabantu “abayimifino”.Ngaphezu komqondo wemvelo, amaphilisi angenalutho angewona awesilwane nawo anezici zawo zobuchwepheshe ezihlukile.Isibonelo, ama-capsules angenalutho e-HPMC anokuqukethwe kwamanzi aphansi kakhulu kanye nokuqina okuhle, futhi afanele okuqukethwe nge-hygroscopicity kanye nokuzwela kwamanzi;I-pullulan hollow capsule ihlakazeka ngokushesha futhi inomoya-mpilo ophansi kakhulu.Ifanele izinto ezinciphisa amandla.Izici ezihlukile zenza imikhiqizo ehlukahlukene yama-capsule angenalutho iphumelele ezimakethe ezithile nezigaba zomkhiqizo.
IZIKHOMBISI
[1] La Wall, CH, 4000 iminyaka ekhemisi, umlando uhlaka lwekhemisi kanye nesayensi ehlangene, JB Lippincott Comp., Philadelphia/London/Montreal, 1940
[2] Feldhaus, FM: Zur Geschichte der Arzneikapsel.I-Dtsch.U-Apoth.-Ztg, 94 (16), 321 (1954)
[3] Französisches Patent Nr.5648, Erteilt am 25. März 1834
[4] Planche und Gueneau de Mussy, Bulletin de I'Académie Royale de Médecine, 442-443 (1837)
[5] U-Graham Cole, Uhlola Izindleko Zokuthuthukiswa Nezokukhiqiza : Amathebulethi Ngokuphikisana Nama-Capsugel.I-Capsugel Library
Isikhathi sokuthumela: May-06-2022