Ihe ntọhapụ-nhapụrụ ọgwụ

01 Cellulose ether

Enwere ike kewaa cellulose n'ime otu ethers na ngwakọta ethers dị ka ụdị ihe nnọchi anya. Enwere naanị otu ụdị nnọchi na otu ether, dị ka methyl cellulose (MC), ethyl cellulose (EC), hydroxyl Propyl cellulose (HPC), wdg; enwere ike ịnwe ihe abụọ ma ọ bụ karịa na ether agwakọta, nke a na-ejikarị eme ihe bụ hydroxypropyl methyl cellulose (HPMC), ethyl methyl cellulose (EMC), wdg. Ihe ndị a na-eji na nkwadebe ọgwụ pulse-release bụ ndị ether HPMC agwakọtara, otu ether HPC, na EC na-anọchi anya ya, bụ nke a na-ejikarị eme ihe dị ka ihe na-agbasa, ihe na-egbuke egbuke, ndị na-azụ azụ na ihe mkpuchi ihe nkiri.

1.1 Hydroxypropylmethylcellulose (HPMC)

N'ihi ogo dị iche iche nke nnọchi nke methoxy na hydroxypropyl otu, HPMC na-ekewakarị n'ime ụdị atọ ná mba ọzọ: K, E na F. N'ime ha, usoro K nwere ọsọ hydration kachasị ọsọ ma dabara dị ka ihe ọkpụkpụ maka ịkwado na njikwa. ntọhapụ nkwadebe. Ọ bụkwa ihe ntọhapụ pulse. Otu n'ime ndị na-ebu ọgwụ a na-ejikarị eme ihe na nkwadebe ọgwụ. HPMC bụ mmiri na-agbaze mmiri na-abụghị ionic cellulose ether, ntụ ntụ ọcha, enweghị ụtọ, isi na adịghị egbu egbu, a na-ewepụkwa ya n'enweghị mgbanwe ọ bụla na ahụ mmadụ. Ọ na-esighi ike na mmiri ọkụ karịa 60°C na nwere ike ịza; mgbe a na-agwakọta ihe ndị na-emepụta ya na viscosities dị iche iche n'ụdị dị iche iche, njikọ njikọ ahụ dị mma, na gel kpụrụ nwere ike ịchịkwa mgbasa nke mmiri na ịhapụ ọgwụ.

HPMC bụ otu n'ime ihe ndị a na-ejikarị eme ihe na-adabere na ọzịza ma ọ bụ usoro ntọhapụ ọgwụ na-achịkwa mbuze na sistemụ ntọhapụ pulse. Ntọhapụ ọgwụ na-aza bụ iji kwadebe ihe ndị na-emepụta ọgwụ na-arụsi ọrụ ike n'ime mbadamba nkume ma ọ bụ pellets, na mkpuchi multi-layer, oyi akwa nke dị n'elu bụ mmiri na-adịghị edozi ma mmiri na-ekpuchi polymer, nke dị n'ime bụ polymer nwere ikike ọzịza, mgbe mmiri na-abanye n'ime ya. oyi akwa dị n'ime, ọzịza ga-emepụta nrụgide, mgbe oge ụfọdụ gasịrị, ọgwụ ahụ ga-agbaze ma na-achịkwa ịhapụ ọgwụ ahụ; ebe ọgwụ ntọhapụ erosion bụ site na ngwugwu ọgwụ bụ isi. Mkpuchi na mmiri na-adịghị ike ma ọ bụ polima na-emebi emebi, na-edozi oke mkpuchi iji chịkwaa oge ntọhapụ ọgwụ.

Ụfọdụ ndị na-eme nchọpụta enyochala ntọhapụ na mmụba e ji mara mbadamba nkume dabeere na hydrophilic HPMC, na chọpụtara na ntọhapụ ọnụego bụ 5 ugboro nwayọọ nwayọọ karịa nke nkịtị mbadamba na nwere bukwanu mgbasawanye.

Ka nwere onye na-eme nchọpụta iji pseudoephedrine hydrochloride dị ka ọgwụ nlereanya, na-agbaso usoro mkpuchi akọrọ, kwadebe akwa oyi akwa na HPMC nke viscosities dị iche iche, gbanwee ntọhapụ nke ọgwụ. Nsonaazụ nke nnwale vivo gosiri na n'okpuru otu ọkpụrụkpụ, obere viscosity HPMC nwere ike iru ọnụ ọgụgụ kasị elu na 5h, ebe elu viscosity HPMC ruru elu ịta n'ihe dị ka 10h. Nke a na-egosi na mgbe a na-eji HPMC eme ihe dị ka ihe mkpuchi, viscosity ya nwere mmetụta dị ịrịba ama na omume ntọhapụ ọgwụ.

Ndị ọrụ nyocha ahụ jiri verapamil hydrochloride dị ka ọgwụ ihe atụ iji dozie mbadamba ụrọ mbadamba okpukpu atọ nke okpukpu abụọ, wee nyochaa usoro ọgwụgwọ HPMC K4M dị iche iche (15%, 20%, 25%, 30%, 35%, w / w; 4M). Na-ezo aka na mmetụta nke viscosity (4000 centipoise) na oge nkwụsịtụ na-egosi na mmụba nke ego HPMC K4M, a na-agbatị oge oge na 4 ruo 5 awa, ya mere HPMC K4M Achọpụtara ọdịnaya ka ọ bụrụ 25%.

1.2 Hydroxypropylcellulose (HPC)

Enwere ike kewaa HPC ka ọ bụrụ hydroxypropyl cellulose dị ala dochie anya (L-HPC) na hydroxypropyl cellulose dị elu dochie anya (H-HPC). L-HPC bụ onye na-abụghị ionic, ọcha ma ọ bụ na-acha ọcha ntụ ntụ, enweghị isi na enweghị ụtọ, ọ bụkwa ihe na-emepụta cellulose na-adịghị egbu egbu nke na-adịghị njọ na ahụ mmadụ. N'ihi na L-HPC nwere nnukwu ebe dị elu na porosity, ọ nwere ike ịmịnye mmiri ngwa ngwa ma zaa, na mmụba mmịnye mmiri ya bụ 500-700%. Banye n'ime ọbara, n'ihi ya, ọ nwere ike kwalite ntọhapụ nke ọgwụ na multi-layer mbadamba na pellet isi, na ukwuu mma curative mmetụta.

Na mbadamba nkume ma ọ bụ pellets, ịgbakwụnye L-HPC na-enyere ndị isi mbadamba (ma ọ bụ pellet core) aka ịgbasa iji mepụta ike dị n'ime, nke na-agbaji mkpuchi mkpuchi ma hapụ ọgwụ ahụ na usu. Ndị nchọpụta ahụ jiri sulpiride hydrochloride, metoclopramide hydrochloride, diclofenac sodium, na nilvadipine mee ihe dị ka ọgwụ nlereanya, na hydroxypropyl cellulose dị ala dochie anya (L-HPC) dị ka onye na-ekesa. The nnwale gosiri na ọkpụrụkpụ nke ọzịza oyi akwa na-ekpebi urughuru size. oge laa azụ.

Ndị nyocha ahụ jiri ọgwụ mgbochi hypertensive dị ka ihe ọmụmụ. N'ime nnwale ahụ, L-HPC dị na mbadamba nkume na capsules, nke mere na ha na-amịkọrọ mmiri wee mebie iji hapụ ọgwụ ahụ ngwa ngwa.

Ndị na-eme nchọpụta na-eji terbutaline sulfate pellets dị ka ọgwụ nlereanya, na nyocha nke mbụ gosiri na iji L-HPC dị ka ihe eji eme ihe n'ime mkpuchi mkpuchi ma na-agbakwụnye SDS kwesịrị ekwesị na mkpuchi mkpuchi n'ime nwere ike nweta mmetụta ntọhapụ pulse a na-atụ anya ya.

1.3 Ethyl cellulose (EC) na mgbasa mmiri ya (ECD)

EC bụ ihe na-abụghị ionic, cellulose alkyl ether nke mmiri na-adịghị edozi, nke nwere njirimara nke nguzogide kemịkalụ, nguzogide nnu, nkwụsi ike alkali na nkwụsi ike okpomọkụ, ma nwee nnukwu viscosity (arọ molekụla) na arụmọrụ dị mma, nwere ike ịmepụta a mkpuchi oyi akwa na ezi siri ike na ọ dịghị mfe iyi, nke na-eme ka ọ na-eji ọtụtụ ebe na ọgwụ kwadoro na-achịkwa ntọhapụ film mkpuchi.

ECD bụ usoro dị iche iche nke ethyl cellulose na-akwụsịtụ n'ime ebe a na-ekesa (mmiri) n'ụdị obere ụmụ irighiri colloidal ma nwee ezigbo nkwụsi ike anụ ahụ. A na-eji polymer soluble mmiri nke na-arụ ọrụ dị ka onye na-emepụta ihe na-emepụta pore iji dozie ọnụego ntọhapụ nke ECD iji mezuo ihe a chọrọ maka ntọhapụ ọgwụ na-adịgide adịgide maka nkwado ntọhapụ.

EC bụ ihe dị mma maka nkwadebe nke capsules na-abụghị mmiri soluble. Ndị nchọpụta ahụ jiri dichloromethane / absolute ethanol / ethyl acetate (4 / 0.8 / 0.2) dị ka ihe mgbaze na EC (45cp) iji kwadebe 11.5% (w / v) EC ngwọta, kwadebe EC capsule ahụ, ma kwadebe capsule EC na-abụghị permeable. imezu ihe achọrọ maka ntọhapụ pulse ọnụ. Ndị nchọpụta ahụ jiri theophylline dị ka ọgwụ nlereanya iji mụọ mmepe nke usoro pulse multiphase nke ejiri ethyl cellulose aqueous dispersion kpuchie. Nsonaazụ gosiri na ụdị Aquacoat® dị na ECD na-esighi ike ma dị mfe imebi, na-ahụ na enwere ike ịhapụ ọgwụ ahụ n'ọkpụkpụ.

Tụkwasị na nke ahụ, ndị nchọpụta nyochara pellets ntọhapụ na-achịkwa usu nke a kwadebere na mgbasa mmiri ethyl cellulose dị ka oyi akwa mkpuchi mpụta. Mgbe uru dị arọ nke mkpuchi mkpuchi dị n'elu dị 13%, a na-enweta ntọhapụ ọgwụ na-ejikọta ya na oge nkwụsị nke 5 h na oge nkwụsị nke 1.5 h. Ihe karịrị 80% nke mmetụta ntọhapụ pulse.

02 resin acrylic

Acrylic resin bụ ụdị ngwakọta polymer kpụrụ site na copolymerization nke acrylic acid na methacrylic acid ma ọ bụ esters ha n'otu akụkụ. Resin acrylic nke a na-ejikarị bụ Eudragit dị ka aha ahia ya, nke nwere ezigbo ihe na-emepụta ihe nkiri ma nwee ụdị dị iche iche dị ka ụdị gastric-soluble E, ụdị enteric-soluble L, S, na mmiri na-adịghị ike RL na RS. N'ihi na Eudragit nwere uru nke ọmarịcha ihe nkiri na-arụ ọrụ yana ezigbo ndakọrịta n'etiti ụdị dị iche iche, ejiri ya mee ihe na mkpuchi ihe nkiri, nkwadebe matriks, microspheres na sistemụ ntọhapụ ndị ọzọ.

Ndị nchọpụta ahụ jiri nitrendipine mee ihe dị ka ọgwụ nlereanya na Eudragit E-100 dị ka ihe dị mkpa iji kwadebe pellets nwere mmetụta pH, ma nyochaa bioavailability ha na nkịta nwere ahụike. Nsonaazụ nke ọmụmụ ahụ chọpụtara na nhazi akụkụ atọ nke Eudragit E-100 na-enyere ya aka ịhapụ ngwa ngwa n'ime nkeji 30 n'okpuru ọnọdụ acidic. Mgbe pellets dị na pH 1.2, oge nkwụsị bụ awa 2, na pH 6.4, oge nkwụsị bụ awa 2, na pH 7.8, oge nkwụsị bụ awa 3, nke nwere ike ịghọta nchịkwa ntọhapụ na-achịkwa na eriri afọ.

Ndị nchọpụta ahụ mere nha nke 9: 1, 8: 2, 7: 3 na 6: 4 na ihe ndị a na-emepụta ihe nkiri Eudragit RS na Eudragit RL n'otu n'otu, wee chọpụta na oge ahụ bụ 10h mgbe nhazi ahụ bụ 9: 1. , na oge lagwara bụ 10h mgbe ruru bụ 8:2. Oge nkwụsị oge bụ 7h na 2, oge nkwụsị na 7:3 bụ 5h, na oge nkwụsị na 6:4 bụ 2h; n'ihi na porogens Eudragit L100 na Eudragit S100, Eudragit L100 nwere ike nweta pulse nzube nke 5h oge lag na pH5-7 gburugburu ebe obibi; 20%, 40% na 50% nke ngwọta mkpuchi, achọpụtara na ngwọta mkpuchi nke nwere 40% EudragitL100 nwere ike izute oge achọrọ; Ọnọdụ ndị dị n'elu nwere ike nweta ebumnuche nke oge nkwụsị nke 5.1 h na pH 6.5 na oge ntọhapụ pulse nke 3 awa.

03 Polyvinylpyrrolidones (PVP)

PVP bụ ihe na-abụghị ionic mmiri-soluble polymer compoundized sitere na N-vinylpyrrolidone (NVP). A na-ekewa ya na akara ule anọ dịka nkezi ịdị arọ molekụla ya. A na-egosipụtakarị ya site na uru K. Ka viscosity dị ukwuu, otú ahụ ka adhesion na-esiwanye ike. PVP gel (ntụ ntụ) nwere mmetụta adsorption siri ike na ọtụtụ ọgwụ. Mgbe ịbanye n'afọ ma ọ bụ ọbara, n'ihi ihe onwunwe ọzịza ya dị oke elu, a na-ahapụ ọgwụ ahụ nwayọọ nwayọọ. Enwere ike iji ya dị ka ezigbo onye ntọhapụ na-akwado na PDDS.

Verapamil pulse osmotic mbadamba bụ mbadamba osmotic mbadamba atọ, nke ime oyi akwa bụ nke hydrophilic polymer PVP dị ka push oyi akwa, na hydrophilic ihe na-etolite a hydrophilic gel mgbe ọ zutere mmiri, nke na-akwụsị ntọhapụ ọgwụ, na-enweta oge lag, na na-akwali akwa oyi akwa na-agbasi ike mgbe ọ na-ezute mmiri, na-ebupụ ọgwụ ahụ n'ime oghere ntọhapụ, na nrụgide osmotic bụ isi ihe na-eme ka ihe ịga nke ọma nke nhazi ahụ.

Ndị nyocha ahụ jiri mbadamba verapamil hydrochloride a na-achịkwa na-ahapụ ya dị ka ọgwụ nlereanya, ma jiri PVP S630 na PVP K90 nwere viscos dị iche iche dị ka ihe mkpuchi na-achịkwa. Mgbe uru ihe nkiri ahụ dị 8%, oge nkwụsị (tlag) iji ruo ntọhapụ in vitro bụ awa 3-4, na nkezi ntọhapụ (Rt) bụ 20-26 mg / h.

04 Hydrogel

4.1. Alginic acid

Alginic acid na-acha ọcha ma ọ bụ ntụ ntụ na-acha odo odo, enweghị isi na enweghị ụtọ, cellulose sitere n'okike na-esighi ike na mmiri. Usoro sol-gel dị nro na ezigbo biocompatibility nke alginic acid kwesịrị ekwesị maka ịmepụta microcapsules na-ahapụ ma ọ bụ tinye ọgwụ, protein na sel - ụdị usoro ọgwụgwọ ọhụrụ na PDDS n'afọ ndị na-adịbeghị anya.

Ndị nchọpụta ahụ jiri dextran mee ihe dị ka ọgwụ nlereanya na calcium alginate gel dị ka onye na-ebu ọgwụ iji mee nkwadebe pulse. Nsonaazụ Ọgwụ nke nwere oke molekụla dị elu gosipụtara ntọhapụ oge-lag-pulse, yana enwere ike gbanwee oge ahụ site na ọkpụrụkpụ nke ihe nkiri mkpuchi.

Ndị nchọpụta ahụ jiri sodium alginate-chitosan mepụta microcapsules site na mmekọrịta electrostatic. Nnwale na-egosi na microcapsules nwere ezi nzaghachi pH, ntọhapụ efu na pH=12, na ntọhapụ pulse na pH=6.8. Ụdị ntọhapụ Form S, enwere ike iji dị ka pH na-anabata pulsatile nhazi.

4.2. Polyacrylamide (PAM) na mmepụta ya

PAM na usoro ya bụ polymer molekụla dị elu nke na-agbaze mmiri, nke a na-ejikarị na usoro ntọhapụ pulse. Hydrogel nke na-ekpo ọkụ na-ekpo ọkụ nwere ike ịgbasa ma gbasaa (mkpọtụ) site na mgbanwe nke okpomọkụ dị n'èzí, na-eme ka mgbanwe dị na njedebe, si otú ahụ Iji mezuo nzube nke ịchịkwa ntọhapụ ọgwụ.

Ihe kacha mụọ bụ N-isopropylacrylamide (NIPAAm) hydrogel, nke nwere ebe mgbaze dị egwu (LCST) nke 32.°C. Mgbe okpomọkụ dị elu karịa LCST, gel na-ebelata, na ihe mgbaze dị na netwọk netwọk na-apụ apụ, na-ahapụ nnukwu ihe ngwọta mmiri nke nwere ọgwụ ọjọọ; mgbe okpomọkụ dị ala karịa LCST, gel nwere ike ịmaliteghachi, na mmetụta okpomọkụ nke NPAAm gel nwere ike iji dozie omume ọzịza, nha gel, ọdịdị, wdg iji nweta kpọmkwem "na-apụ" ọgwụ ntọhapụ okpomọkụ na Ọnụego mwepụta ọgwụ thermosensitive hydrogel pulsatile na-achịkwa ntọhapụ.

Ndị nyocha ahụ jiri ngwakọta nke hydrogel na-enwe mmetụta okpomọkụ (N-isopropylacrylamide) na superferric iron tetroxide particles dị ka ihe. A na-agbanwe usoro netwọkụ nke hydrogel, si otú a na-eme ka mwepụta ọgwụ ahụ dịkwuo elu ma nweta mmetụta nke ntọhapụ pulse.

05 edemede ndị ọzọ

Na mgbakwunye na ojiji a na-ejikarị ihe polymer omenala dị ka HPMC, CMS-Na, PVP, Eudragit, na Surlease, ihe ndị ọzọ na-ebu ibu dị ka ọkụ, ọkụ eletrik, oghere magnetik, ultrasonic ebili mmiri, na nanofibers na-anọgide na-emepụta. Dịka ọmụmaatụ, a na-eji liposome sonic-sensitive eme ihe dị ka onye na-ebu ọgwụ site n'aka ndị nchọpụta, na mgbakwunye nke ultrasonic ebili mmiri nwere ike ime ka obere gas dị na sonic-sensitive liposome, nke mere na a na-ahapụ ọgwụ ahụ ngwa ngwa. Ndị na-eme nchọpụta na TPPS na ChroB jiri electrospun nanofibers mee ihe iji chepụta usoro nhazi akụkụ anọ, na ntọhapụ pulse nwere ike mezuo na simulated na vivo gburugburu ebe obibi nwere 500.μg/ml protease, 50mM hydrochloric acid, pH8.6.