Ka-faa'iideystayaasha sii-daynta joogtada ah ee Dawooyinka

01 Cellulose ether

Cellulose waxaa loo qaybin karaa hal ethers iyo ethers isku dhafan iyadoo loo eegayo nooca beddelka. Hal nooc oo beddel ah ayaa ku jira hal ether, sida methyl cellulose (MC), ethyl cellulose (EC), hydroxyl Propyl cellulose (HPC), iwm.; waxaa jiri kara laba ama in ka badan oo beddel ah oo ku jira ether-ka isku dhafan, sida caadiga ah loo isticmaalo waa hydroxypropyl methyl cellulose (HPMC), ethyl methyl cellulose (EMC), iwm. Kaabayaasha loo isticmaalo diyaarinta daawada garaaca garaaca waxaa ka mid ah ether HPMC isku qasan, hal ether HPC, iyo EC, kuwaas oo inta badan loo isticmaalo sida kala daadsanaan, wakiilada bararka, dib-u-celinta, iyo alaabta daahan filimada.

1.1 Hydroxypropylmethylcellulose (HPMC)

Sababtoo ah heerarka kala duwan ee beddelka kooxaha methoxy iyo hydroxypropyl, HPMC guud ahaan waxaa loo qaybiyaa saddex nooc oo dibadda ah: K, E iyo F. Waxaa ka mid ah, taxanaha K wuxuu leeyahay xawaaraha fuuq-celinta ugu dhaqsaha badan wuxuuna ku habboon yahay qalab qalfoof ah oo joogto ah oo la xakameeyo. sii daayo diyaarinta. Sidoo kale waa wakiilka garaaca wadnaha. Mid ka mid ah dawooyinka sida caadiga ah loo isticmaalo diyaarinta dawooyinka. HPMC waa unug-cellulose aan-ionic ahayn oo biyo-milmi kara, budo cad, aan dhadhamin, ur lahayn oo aan sun ahayn, waxaana la soo saaraa iyada oo aan wax isbeddel ah ku dhicin jidhka bini'aadamka. Asal ahaan kuma milmi karaan biyaha kulul ee ka sarreeya 60°C oo kaliya ayaa barari kara; marka ay ka-soo-saarkeeda leh viscosities kala duwan ay isku dhafan yihiin qaybo kala duwan, xiriirka toosan waa wanaagsan yahay, jel la sameeyay ayaa si wax ku ool ah u xakameyn kara faafinta biyaha iyo sii deynta daroogada.

HPMC waa mid ka mid ah walxaha polymer-ka ee sida caadiga ah loo isticmaalo oo ku salaysan bararka ama habka lagu sii daayo nabaadguurka ee la xakameeyey ee habka siideynta garaaca wadnaha. Siidaynta daawada bararka waa in la diyaariyo maaddooyinka dawooyinka firfircoon ee kiniiniyada ama pellets, ka dibna daahan lakabyo badan, lakabka sare waa Biyo-la'aan laakiin daahan polymer-ka ah ee biyaha, lakabka gudaha waa polymer leh awood barar, marka dareeruhu galo gudaha. lakabka gudaha, bararka ayaa dhalin doona cadaadis, ka dib wakhti, daawadu way barari doontaa oo la xakameynayaa si loo sii daayo daawada; halka dawada sii daynta nabaadguurku ay tahay iyada oo loo marayo xidhmada daawada asaasiga ah. Dahaarka leh polymers-biyoodka-aan-milmi karin ama nabaad-guurka, hagaajinta dhumucda dahaarka si loo xakameeyo wakhtiga siideynta daroogada.

Cilmi-baadhayaasha qaarkood ayaa baadhay sifooyinka sii-deynta iyo fidinta kiniinnada ee ku salaysan hydrophilic HPMC, waxayna ogaadeen in heerka sii-deynta uu 5 jeer ka yar yahay kan kiniinnada caadiga ah oo uu leeyahay balaadhin la taaban karo.

Weli waxay leeyihiin cilmi-baadhaha si ay u isticmaalaan pseudoephedrine hydrochloride sida daawada model, qaataan habka daahan qalalan, diyaarin lakabka jaakad HPMC of viscosities kala duwan, hagaajin sii daayo daawada. Natiijooyinka tijaabooyinka vivo waxay muujiyeen in dhumucdiis la mid ah, hoos-u-muuqaalka HPMC uu ku gaari karo diiradda ugu sarreysa 5h, halka HPMC-muuqaalka-sare uu gaaray diiradda ugu sarreysa qiyaastii 10h. Tani waxay soo jeedinaysaa in marka HPMC loo isticmaalo sida walax dahaar ah, viscosity-kiisu uu saameyn weyn ku yeelanayo habdhaqanka sii deynta daroogada.

Cilmi-baadhayaashu waxay isticmaaleen daawada loo yaqaan 'verapamil hydrochloride' si ay u diyaariyaan kiniiniyada koobabka kiniiniga ah ee saddex-lakabka ah, waxayna baareen qiyaasaha kala duwan ee HPMC K4M (15%, 20%, 25%, 30%, 35%, w/w; 4M) Waxa loola jeedaa saamaynta viscosity (4000 centipoise) ee wakhtiga dib u dhaca Natiijooyinku waxay muujinayaan in kororka cadadka HPMC K4M, wakhtiga dib u dhaca ayaa lagu wadaa 4 ilaa 5 saacadood, sidaas darteed HPMC K4M waxa ku jira waxa lagu go'aamiyay in ay tahay 25%.

1.2 Hydroxypropylcellulose (HPC)

HPC waxa loo qaybin karaa hydroxypropyl cellulose (L-HPC) oo la bedelay-hoose iyo hydroxypropyl cellulose (H-HPC). L-HPC waa budo aan-ionic ahayn, caddaan ama cad-cad, aan ur lahayn oo aan dhadhamin, waana mid dhexdhexaad ah oo aan waxyeello u geysan jidhka bini'aadamka. Sababtoo ah L-HPC waxay leedahay aag weyn oo dusha sare ah iyo porosity, waxay si dhakhso ah u nuugi kartaa biyaha oo barari, iyo heerka nuugista biyuhu waa 500-700%. Geli dhiiga, si ay kor ugu qaaddo sii deynta daawada ee kiniiniga lakabka badan iyo xudunta pellet, oo si weyn u wanaajiso saameynta daaweynta.

Kiniinada ama pellets, ku darida L-HPC waxay caawisaa xudunta kiniinka (ama pellet core) si ay u balaariso si ay u abuurto xoog gudaha ah, kaas oo jebiya lakabka daahan oo sii daaya daawada garaaca wadnaha. Cilmi-baadhayaashu waxay isticmaaleen sulpiride hydrochloride, metoclopramide hydrochloride, diclofenac sodium, iyo nilvadipine sida daawooyinka moodeelka ah, iyo hydroxypropyl cellulose oo hooseeya (L-HPC) oo beddelaad ah sida wakiilka kala daadsan. Tijaabooyinku waxay muujiyeen in dhumucda lakabka bararka ay go'aamiso xajmiga qaybta. waqti dib u dhac.

Cilmi-baarayaashu waxay u isticmaaleen dawooyinka ka hortagga hypertensive shayga daraasadda. Tijaabada, L-HPC waxay ku jirtay kiniinnada iyo kaabsaloyinka, si ay u nuugaan biyaha ka dibna u nabaadguuraan si ay si dhakhso ah u sii daayaan daawada.

Cilmi-baadhayaashu waxay adeegsadeen pellets terbutaline sulfate sida daroogada moodeelka ah, iyo natiijooyinka tijaabada hordhaca ah waxay muujiyeen in isticmaalka L-HPC sida walxaha lakabka gudaha iyo ku darida SDS ku habboon lakabka gudaha gudaha waxay gaari kartaa saameynta sii deynta garaaca wadnaha ee la filayo.

1.3 Ethyl cellulose (EC) iyo kala firdhiskeeda aqueous (ECD)

EC waa non-ionic, cellulose alkyl ether-biyo-la'aan, kaas oo leh sifooyinka caabbinta kiimikada, caabbinta milixda, caabbinta alkali iyo xasiloonida kulaylka, oo uu leeyahay tiro balaadhan oo ah viscosity (miisaanka kelli) iyo waxqabadka dharka wanaagsan, samayn karaa a lakabka dahaarka leh adkeysi wanaagsan oo ma fududa in la xidho, taas oo ka dhigaysa in si weyn loogu isticmaalo dahaarka filimka sii daayo ee joogtada ah iyo la xakameeyey.

ECD waa nidaam kala duwan kaas oo ethyl cellulose uu ku xayiran yahay meel kala firdhiso (biyaha) qaab qaybo yaryar oo kolloidal ah oo leh xasillooni jireed oo wanaagsan. Polymer-ka biyaha ku milma oo u shaqeeya sidii wakiilka dalool-samaynta ayaa loo isticmaalaa in lagu hagaajiyo heerka siideynta ECD si loo buuxiyo shuruudaha sii deynta daawada joogtada ah ee diyaarinta sii-deynta joogtada ah.

EC waa wax ku habboon diyaarinta kaabsal aan biyo-milmi karin. Cilmi-baadhayaashu waxay isticmaaleen dichloromethane / absolute ethanol / ethyl acetate (4 / 0.8 / 0.2) sida dareeraha iyo EC (45cp) si ay u diyaariyaan 11.5% (w / v) EC xal, u diyaariyaan jirka kaabsoosha EC, iyo diyaarinta kaabsoosha EC ee aan la daadin karin buuxinta shuruudaha siidaynta garaaca afka. Cilmi-baadhayaashu waxay isticmaaleen theophylline sida daroogada moodeelka ah si ay u daraaseeyaan horumarinta nidaamka garaaca wadnaha ee wejiga badan oo lagu dahaadhay faafinta aqueous ethyl cellulose. Natiijooyinka waxay muujiyeen in noocyada Aquacoat® ee ECD ay yihiin kuwo jilicsan oo sahlan in la jebiyo, hubinta in daawada lagu sii daayo garaaca wadnaha.

Intaa waxaa dheer, cilmi-baarayaashu waxay daraasad ku sameeyeen pellets-ka-xakamaynta garaaca wadnaha oo lagu diyaariyey faafinta aqueous ethyl cellulose sida lakabka daboolka dibadda. Marka korodhka miisaanka lakabka daahan dibadda ah uu ahaa 13%, sii daynta daawada isugaynta ah ayaa lagu gaadhay dib u dhac ku yimid 5 h iyo wakhtiga 1.5 h. In ka badan 80% saamaynta sii daynta garaaca wadnaha.

02 xabagta akril

Xabagta acrylic waa nooc ka mid ah xeryahooda polymer ee lagu sameeyay isku-duubnida acrylic acid iyo methacrylic acid ama ester-kooda qayb ahaan. Daawada loo yaqaan 'acrylic resin' ee sida caadiga ah loo isticmaalo waa Eudragit oo ah magaca ganacsiga, kaas oo leh sifooyin filim samaynta oo wanaagsan oo leh noocyo kala duwan sida nooca E gastric-soluble E, nooca L, nooca S, iyo RL-biyood-la'aanta. Sababtoo ah Eudragit waxay leedahay faa'iidooyinka waxqabadka filim samaynta fiican iyo iswaafajinta wanaagsan ee moodooyinka kala duwan, waxaa si weyn loogu isticmaalay daaha filimka, diyaarinta matrixka, microspheres iyo nidaamyada kale ee sii deynta garaaca wadnaha.

Cilmi-baadhayaashu waxay u isticmaaleen nitrendipine sida daroogada moodeelka ah iyo Eudragit E-100 oo ah faa'iido muhiim ah si loogu diyaariyo pellets xasaasiga ah ee pH, waxayna qiimeeyeen bioavailability ee eeyaha caafimaadka qaba. Natiijooyinka daraasadda ayaa lagu ogaaday in qaabdhismeedka saddex-geesoodka ah ee Eudragit E-100 uu awood u siinayo in si degdeg ah loo sii daayo 30 daqiiqo gudahood xaaladaha acidic. Marka pellets ay ku jiraan pH 1.2, wakhtigu waa 2 saacadood, pH 6.4, wakhtigu waa 2 saacadood, iyo pH 7.8, wakhtigu waa saacadaha 3, taas oo xaqiijin karta maamulka siideynta la xakameeyey ee marinka mindhicirka.

Cilmi-baadhayaashu waxay sameeyeen saamiga 9: 1, 8: 2, 7: 3 iyo 6: 4 ee walxaha samaynta filimka Eudragit RS iyo Eudragit RL siday u kala horreeyaan, waxayna ogaadeen in wakhtigu uu ahaa 10h marka saamiga uu ahaa 9: 1 , wakhtiguna waxa uu ahaa 10h marka saamigu ahaa 8:2. Wakhtigu waa 7:00 saacadu markay tahay 2, wakhtigu waa 7:3 waa 5h, wakhtiga 6:4 waa 2h loogu talagalay porogens Eudragit L100 iyo Eudragit S100, Eudragit L100 waxay gaari kartaa ujeedada garaaca wadnaha ee wakhtiga 5h ee deegaanka pH5-7; 20%, 40% iyo 50% ee xal daahan, waxaa la ogaaday in xal daahan ka kooban 40% EudragitL100 buuxin kartaa shuruudaha wakhtiga; Shuruudaha kor ku xusan waxay gaari karaan ujeedada dib u dhaca wakhtiga 5.1 h ee pH 6.5 iyo wakhtiga sii deynta garaaca wadnaha oo ah 3 saacadood.

03 Polyvinylpyrrolidones (PVP)

PVP waa iskudarka polymer-ka ee aan-ionic-ka ahayn ee biyaha ku milma, polymerized laga sameeyay N-vinylpyrrolidone (NVP). Waxa loo qaybiyaa afar darajo iyadoo loo eegayo celceliska miisaankiisa kelli. Waxaa badanaa lagu muujiyaa qiimaha K. Markasta oo uu ba'an yahay viscosity, ayaa sii xoogeysanaya adhesion-ka. PVP jel (budada) waxay saameyn xoog leh ku leedahay daawooyinka badankood. Ka dib markaad gasho caloosha ama dhiigga, sababtoo ah hantideeda bararka aadka u sarreeya, dawada si tartiib ah ayaa loo sii daayaa. Waxa loo isticmaali karaa sidii wakiilka sii daynta heersare ee PDDS.

Kiniiniga Verapamil pulse osmotic waa kiniin saddex-lakab ah oo osmotic ah, lakabka gudaha wuxuu ka samaysan yahay hydrophilic polymer PVP oo ah lakabka riixida, walaxda hydrophilic waxay samaysaa jel hydrophilic marka ay la kulanto biyaha, taas oo dib u dhigaysa sii deynta daroogada, waxay heleysaa dib u dhac, iyo riixdo Lakabku si xoog leh ayuu u bararaa marka uu la kulmo biyaha, isaga oo ka riixaya dawada ka soo baxa daloolka sii deynta, iyo cadaadiska osmotic-ga ayaa fure u ah guusha samaynta.

Cilmi-baadhayaashu waxay isticmaaleen kiniinnada la xakameeyey ee verapamil hydrochloride sida dawooyin moodal ah, waxayna u isticmaaleen PVP S630 iyo PVP K90 oo leh muuqaalo kala duwan oo ah agabka dahaadhida la xakameeyey. Marka miisaanka filimku uu kordho 8%, wakhtiga (tlag) si loo gaaro sii deynta vitro waa 3-4 saacadood, iyo celceliska heerka sii deynta (Rt) waa 20-26 mg / h.

04 Hydrogel

4.1. Alginic acid

Alginic acid waa budo jaale ah oo cad ama khafiif ah, aan ur lahayn oo aan dhadhamin, cellulose dabiici ah oo aan lagu milmin biyaha. Habka sol-gel fudud iyo biocompatibility wanaagsan ee alginic acid waxay ku habboon yihiin samaynta kaabsuulyada yaryar ee sii daaya ama ku dhejinaya daroogooyinka, borotiinka iyo unugyada - qaab qiyaaseed cusub oo PDDS ah sanadihii ugu dambeeyay.

Cilmi-baadhayaashu waxay isticmaaleen dextran sida daroogada moodada ah iyo calcium alginate gel sida side daroogada si ay u sameeyaan diyaarinta garaaca wadnaha. Natiijooyinka Daawada leh miisaan sare oo kelli ah ayaa muujisay sii daynta wakhtiga-dab-daaca, iyo wakhtiga dib u dhaca waxa lagu hagaajin karaa dhumucda filimka daahan.

Cilmi-baadhayaashu waxay isticmaaleen sodium alginate-chitosan si ay u sameeyaan microcapsules iyada oo loo marayo isdhexgalka elektrostatic. Tijaabooyinku waxay muujinayaan in microcapsules-ku ay leeyihiin jawaab celin wanaagsan oo pH ah, siidaynta eber ee pH=12, iyo sii deynta garaaca wadnaha pH=6.8. Qalooca siideynta Form S, waxa loo isticmaali karaa qaab pH-ka jawaab celinta garaaca wadnaha.

4.2. Polyacrylamide (PAM) iyo asalkiisa

PAM iyo ka-soo-saarkeedu waa polymers-molecular sare oo biyo-milmi kara, kuwaas oo inta badan loo isticmaalo nidaamka sii-deynta garaaca wadnaha. Hydrogel-xasaasiga ah ee kulaylka ayaa dib u balaarin kara oo demin kara (yaray) iyada oo isbeddelka heerkulka dibedda, uu keeno isbeddel ku yimaada xajinta, si loo gaaro ujeedada xakamaynta sii deynta daroogada.

Midda ugu badan ee la bartay waa N-isopropylacrylamide (NIPAAm) hydrogel, oo leh barta dhalaalka muhiimka ah (LCST) ee 32°C. Marka heerkulku ka sarreeyo LCST, jelku wuu yaraadaa, dareeraha ku jira qaab dhismeedka shabakada waa la tuujiyaa, isagoo siidaaya qadar badan oo ah xal aqueous ah oo ay ku jirto Maandooriyaha; marka heerkulku ka hooseeyo LCST, jelku dib wuu barari karaa, dareenka heerkulka NPAAm gel waxa loo isticmaali karaa in lagu hagaajiyo habdhaqanka bararka, cabbirka jelka, qaabka, iwm. Qiyaasta siideynta dawada qaabaynta heerkulbeegga hydrogel pulsatile la xakameeyey.

Cilmi-baadhayaashu waxay isticmaaleen isku-dhafka hydrogel-xasaasiga ah (N-isopropylacrylamide) iyo walxaha tetroxide ee birta ee superferric. Qaab dhismeedka shabakadda ee hydrogel waa la beddelaa, taas oo dardargelinaysa sii deynta daroogada iyo helitaanka saameynta sii deynta garaaca wadnaha.

05 qaybaha kale

Marka lagu daro isticmaalka baahsan ee alaabada polymer-ka ah sida HPMC, CMS-Na, PVP, Eudragit, iyo Surlease, agabyada kale ee sidayaal cusub sida iftiinka, korontada, meelaha magnetic, hirarka ultrasonic, iyo nanofibers ayaa si joogto ah loo horumariyay. Tusaale ahaan, liposome-ka xasaasiga ah ee loo yaqaan 'sonic-sensitive liposome' waxaa loo isticmaalaa sida side daroogada cilmi-baarayaasha, iyo ku darida mowjadaha ultrasonic waxay samayn kartaa qadar yar oo gaas ah oo ku jira dhaqdhaqaaqa xasaasiga ah ee sonic-xasaasi ah, si daawada si dhakhso ah loo sii daayo. Nanofibers-ka elektiroonigga ah waxaa isticmaalay cilmi-baarayaasha TPPS iyo ChroB si ay u naqshadeeyaan qaab dhismeed afar-lakab ah, iyo sii-deynta garaaca wadnaha waxaa lagu xaqiijin karaa jawiga vivo ee ka kooban 500μg/ml protease, 50mM hydrochloric acid, pH8.6.