I-Capsule yenye yeendlela zakudala zedosi yeziyobisi, ezavela eYiputa yamandulo [1].U-De Pauli, usokhemesti waseVienna, okhankanywe kwidayari yakhe yokuhamba ngo-1730 ukuba ii-capsules ze-Oval zazisetyenziselwa ukufihla iphunga elibi lamachiza ukunciphisa intlungu yezigulane [2].Ngaphezulu kweminyaka eyi-100 kamva, oosokhemesti uJoseph Gerard Auguste dublanc kunye noFrancois Achille Barnabe motors bafumana i-patent ye-gelatin capsule yokuqala yehlabathi kwi-1843 kwaye ngokuqhubekayo bayiphucula ukuze ihambelane nemveliso ye-industrial [3,4];Ukusukela ngoko, amalungelo awodwa omenzi wechiza kwii-capsules ezingenanto ziye zazalwa.Ngo-1931, u-Arthur Colton wenkampani yaseParke Davis wayila ngempumelelo kwaye wenza izixhobo zokuvelisa ezizenzekelayo ze-capsule engenanto kwaye wavelisa i-capsule yokuqala yehlabathi eyenziwe ngomatshini.Kuyathakazelisa ukuba ukuza kuthi ga ngoku, umgca wokuvelisa i-capsule ongenanto uphuculwe ngokuqhubekayo kwisiseko soyilo luka-Arthur ukuphucula umgangatho wemveliso kunye nokusebenza kakuhle kwemveliso.
Okwangoku, i-capsule yenze uphuhliso olukhulu kwaye olukhawulezayo kwinkalo yokhathalelo lwempilo kunye nekhemesti, kwaye ibe yenye yeendlela eziphambili zedosi yamalungiselelo aqinileyo omlomo.Ukusukela ngo-1982 ukuya ku-2000, phakathi kwamachiza amatsha avunyiweyo kwihlabathi jikelele, iifom zedosi ye-capsule eqinile zibonise indlela yokunyuka.
Umzobo 1 Ukusukela ngo-1982, amachiza amatsha emolekyuli athelekiswe phakathi kwee-capsules kunye neepilisi
Ngophuhliso lwemveliso yamayeza kunye neshishini le-R & D, izibonelelo ze-capsules ziye zaqatshelwa ngakumbi, ngakumbi kule miba ilandelayo:
1. Ukhetho lwesigulane
Xa kuthelekiswa nezinye iifom zedosi, ii-capsules ezinzima zinokugubungela ngokufanelekileyo iphunga elibi lamachiza kwaye kulula ukugwinya.Imibala eyahlukeneyo kunye noyilo lokushicilela lwenza ukuba iziyobisi zibonakale ngakumbi, ukuze kuphuculwe ngokufanelekileyo ukuthotyelwa kweziyobisi.Kwi-1983, uphando olwenziwa ngabasemagunyeni baseYurophu naseMelika lubonise ukuba phakathi kwezigulane ze-1000 ezikhethiweyo, i-54% ikhetha ii-capsules ezinzima, i-29% yakhetha iipelisi ezifakwe iswekile, i-13% kuphela yakhetha iipilisi, kwaye enye i-4% ayizange ikhethe ngokucacileyo.
2. Ubuchule obuphezulu be-R&D
Ingxelo ye-tufts ka-2003 yabonisa ukuba iindleko zophando lwamachiza kunye nophuhliso zinyuke nge-55% ukusuka ku-1995 ukuya ku-2000, kwaye i-avareji yeendleko zehlabathi zophando lwamachiza kunye nophuhliso lufikelele kwi-897 yezigidi zeedola zaseMelika.Njengoko sisazi sonke, amayeza angaphambili adwelisiwe, kokukhona liya kuba lide ixesha lokuthengisa amayeza anelungelo elilodwa lomenzi, kwaye inzuzo yamachiza amatsha kumashishini axuba amayeza iya konyuka kakhulu.I-avareji yenani le-excipients esetyenziswe kwii-capsules yi-4, eyancitshiswa kakhulu xa kuthelekiswa ne-8-9 kwiipilisi;Izinto zokuvavanya ii-capsules nazo zincinci, kwaye iindleko zokusekwa kwendlela, ukuqinisekiswa kunye nohlalutyo malunga nesiqingatha sepilisi.Ngoko ke, xa kuthelekiswa namacwecwe, ixesha lokuphuhlisa i-capsules lincinci ubuncinane kwisiqingatha sonyaka kuneepilisi.
Ngokubanzi, i-22% yamaqumrhu amatsha adibeneyo kuphando lwechiza kunye nophuhliso anokungena kwisigaba soku-I kulingo lwezonyango, apho ngaphantsi kwe-1 / 4 inokuphumelela kwisigaba sesi-III solingo lwezonyango.Ukuhlolwa kweekhompawundi ezintsha kunokunciphisa ngempumelelo iindleko zophando lwamachiza amatsha kunye namaziko ophuhliso ngokukhawuleza.Ke ngoko, ishishini lehlabathi lokuvelisa i-capsules elingenanto liphuhlise ii-capsules ze-preclinical (pccaps) ezifanelekileyo kwizilingo ze-rodent ®）; Izixhobo zokuzalisa ezichanekileyo ezincinci (i-xcelodose) ezifanelekileyo ukuveliswa kweesampuli ze-capsule zeklinikhi kwizilingo zeklinikhi ezinkulu ®) Kwaye uluhlu olupheleleyo lweemveliso zokuxhasa Ukunciphisa iindleko ze-R & D kunye nokuphucula ukusebenza kakuhle kwe-R & D.
Ukongeza, kukho ngaphezu kwe-9 iintlobo zee-capsules ezinobungakanani obuhlukeneyo, ezibonelela ngokukhetha okuninzi kuyilo lwedosi yeziyobisi.Ukuphuhliswa kwetheknoloji yokulungiselela kunye nezixhobo ezinxulumene nazo kwenza i-capsule ifaneleke kwiikhompawundi ezininzi ezineepropati ezikhethekileyo, ezifana neengqungquthela ezingaxutywanga emanzini.Uhlalutyo lubonisa ukuba i-50% yamaqumrhu amatsha amatsha afunyenwe ngokuhlolwa okuphezulu kunye nekhemistri edibeneyo ayinyibiliki emanzini (20%) μ G / ml), zombini ii-capsules ezizaliswe lulwelo kunye nee-capsules ezithambileyo zinokuhlangabezana neemfuno zolu lungiselelo lwekhompawundi.
3. Iindleko eziphantsi zemveliso
Xa kuthelekiswa namacwecwe, i-workshop ye-GMP yokuvelisa i-capsules enzima ineenzuzo zezixhobo zokusebenza ezincinci, ukusetyenziswa kwendawo ephezulu, ukucwangciswa okunengqiqo ngakumbi, amaxesha angaphantsi kokuhlolwa kwenkqubo yokuvelisa, iiparitha zokulawula umgangatho ophantsi, abaqhubi abancinci, umngcipheko ophantsi wongcoliseko olunqamlezayo, olulula. inkqubo yokulungiselela, iinkqubo ezincinci zokuvelisa, izinto ezincedisayo ezilula kunye neendleko eziphantsi.Ngokoqikelelo lweengcali ezigunyazisiweyo, iindleko ezibanzi zee-capsules ezinzima ziyi-25-30% ephantsi kuneepilisi [5].
Ngophuhliso olunamandla lwee-capsules, ii-capsules ezingenanto, njengenye yezinto eziphambili, nazo zisebenza kakuhle.Ngo-2007, inani lilonke lentengiso yee-capsules ezingenanto kwihlabathi liye ladlula i-310 yezigidigidi, apho i-94% ikwi-gelatin engenanto, ngelixa enye i-6% isuka kwii-capsules ezingezizo izilwanyana, apho izinga lokukhula lonyaka le-hydroxypropyl methylcellulose (HPMC) I-capsules engenanto ingaphezulu kwe-25%.
Ukwanda okumandla kwintengiso yeecapsules ezingezizo izilwanyana zibonakalisa indlela yokusetyenziswa kwemveliso yendalo ehlabathini.EUnited States kuphela, umzekelo, kukho abantu abazizigidi ezingama-70 "abangazange batye iimveliso zezilwanyana", kwaye i-20% yabantu bebonke "yimifuno".Ukongeza kwingqikelelo yendalo, ii-capsules ezingezizo izilwanyana zikwanazo neempawu zobugcisa ezizodwa.Ngokomzekelo, ii-capsules ezingenanto ze-HPMC zinomxholo ophantsi kakhulu wamanzi kunye nokuqina okulungileyo, kwaye zifanelekile kumxholo kunye ne-hygroscopicity kunye novakalelo lwamanzi;I-Pullulan hollow capsule iqhekeka ngokukhawuleza kwaye inokungena kweoksijini ephantsi kakhulu.Ifanelekile kwizinto ezinamandla zokunciphisa.Iimpawu ezahlukeneyo zenza iimveliso ezahlukeneyo ze-capsule ezingenanto ziphumelele kwiimarike ezithile kunye neendidi zeemveliso.
IZIQINISEKISO
[1] La Wall, CH, iminyaka eyi-4000 yekhemesti, inkcazo yembali yekhemesti kunye nesayensi edibeneyo, iJB Lippincott Comp., Philadelphia / London / Montreal, 1940
[2] Feldhaus, FM: Zur Geschichte der Arzneikapsel.Dtsch.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] uGraham Cole, uVavanyo lweNdleko zoPhuhliso kunye neMveliso : IiTablets Versus Capsugels.Capsugel Library
Ixesha lokuposa: May-06-2022