\u00c7ift ta\u015f\u0131y\u0131c\u0131 sistem kullan\u0131larak artemisinin h\u0131zl\u0131 sal\u0131ml\u0131 kat\u0131 dispersiyon haz\u0131rlama s\u00fcrecinin optimizasyonu
\nS\u0131tma, s\u0131tma parazitlerinin neden oldu\u011fu, sivrisinekler taraf\u0131ndan bula\u015ft\u0131r\u0131lan ve d\u00fcnya \u00e7ap\u0131nda yayg\u0131n olarak g\u00f6r\u00fclen olduk\u00e7a \u00f6l\u00fcmc\u00fcl k\u00f6t\u00fc huylu bula\u015f\u0131c\u0131 bir hastal\u0131kt\u0131r. S\u0131tma parazitlerinin d\u00f6ng\u00fcsel bula\u015fmas\u0131 ve karma\u015f\u0131k ya\u015fam d\u00f6ng\u00fcs\u00fc, s\u0131tman\u0131n tamamen ortadan kald\u0131r\u0131lmas\u0131n\u0131 zorla\u015ft\u0131rm\u0131\u015ft\u0131r. Klorokin, kinin, imikin ve piperaquine gibi geleneksel s\u0131tma ila\u00e7lar\u0131n\u0131n \u00e7o\u011fu diren\u00e7 geli\u015ftirmi\u015f ve etkisiz hale gelmi\u015ftir. Artemisinin (ART) s\u0131n\u0131f\u0131 antimalaryal ila\u00e7lar h\u0131zl\u0131 bir etkiye sahiptir ve \u015fu anda d\u00fc\u015f\u00fck toksisiteye sahip oldu\u011fu kabul edilmektedir ve hen\u00fcz belirgin bir diren\u00e7 g\u00f6stermemi\u015f ve birinci basamak antimalaryal ila\u00e7lar haline gelmi\u015ftir. ART, Artemisia annua L. yapraklar\u0131ndan elde edilen bir seskiterpen laktonudur. S\u0131tma tedavisi i\u00e7in sadece birinci basamak antimalaryal ila\u00e7 olmakla kalmaz, ayn\u0131 zamanda antiviral, imm\u00fcn reg\u00fclasyon, anti-inflamatuar, antiparazitik, antifungal ve anti-t\u00fcm\u00f6r gibi \u00e7e\u015fitli biyolojik aktivitelere sahiptir. Bununla birlikte, zay\u0131f su ve lipid \u00e7\u00f6z\u00fcn\u00fcrl\u00fc\u011f\u00fc nedeniyle, in vivo emilimi eksik ve biyoyararlan\u0131m\u0131 d\u00fc\u015f\u00fck, az \u00e7\u00f6z\u00fcn\u00fcr bir ila\u00e7t\u0131r. Artemisinin klinik uygulamas\u0131n\u0131 k\u0131s\u0131tlayan bu sorunlar\u0131 etkili bir \u015fekilde \u00e7\u00f6zmek i\u00e7in, son y\u0131llarda artemisinin bazl\u0131 ila\u00e7 form\u00fclasyonlar\u0131na bir\u00e7ok yeni y\u00f6ntem uygulanm\u0131\u015f ve bunlar\u0131n aras\u0131nda kat\u0131 dispersiyon teknolojisi dikkat \u00e7ekmi\u015ftir.<\/p>\n
Kat\u0131 dispersiyon (SD), kat\u0131 hidrofobik aktif farmas\u00f6tik bile\u015fenlerin kat\u0131 bir hidrofilik inert ta\u015f\u0131y\u0131c\u0131 i\u00e7inde molek\u00fcler veya mikrokristalin halde da\u011f\u0131t\u0131lmas\u0131yla olu\u015fturulan bir dispersiyon sistemidir. \u0130la\u00e7 \u00e7\u00f6z\u00fcn\u00fcrl\u00fc\u011f\u00fcn\u00fc ve \u00e7\u00f6z\u00fcnmesini \u00f6nemli \u00f6l\u00e7\u00fcde art\u0131rabilir, ila\u00e7lar\u0131n oral emilimini te\u015fvik edebilir, biyoyararlan\u0131m\u0131 iyile\u015ftirebilir ve ayr\u0131ca stabil ve y\u00fcksek oranda da\u011f\u0131lm\u0131\u015f ila\u00e7lar elde edebilir veya hatta uygun ta\u015f\u0131y\u0131c\u0131 ve yard\u0131mc\u0131 maddeleri se\u00e7erek s\u00fcrekli ve kontroll\u00fc sal\u0131m etkileri elde edebilir. Ansari ve ark. tek bir ta\u015f\u0131y\u0131c\u0131 olarak PVP K30 kullanarak dihidroartemisinin kat\u0131 bir dispersiyonunu haz\u0131rlam\u0131\u015f ve dihidroartemisinin ta\u015f\u0131y\u0131c\u0131 ile amorf bir kompleks olarak var oldu\u011funu ve \u00e7\u00f6z\u00fcn\u00fcrl\u00fc\u011f\u00fcn\u00fcn aktif farmas\u00f6tik bile\u015fenden 50 kat daha y\u00fcksek oldu\u011funu bulmu\u015ftur; Yang ve ark. en uygun ta\u015f\u0131y\u0131c\u0131 olarak poloksamer 188 kullanarak evodiaminin kat\u0131 bir dispersiyonunu haz\u0131rlam\u0131\u015f, bu da ilac\u0131n i\u00e7eri\u011fini ve morfolojisini etkilemeden \u00e7\u00f6z\u00fcnmesini b\u00fcy\u00fck \u00f6l\u00e7\u00fcde iyile\u015ftirmi\u015ftir; Li ve ark. \u00e7ift ta\u015f\u0131y\u0131c\u0131 olarak PEG 6000 lesitin ve tek ta\u015f\u0131y\u0131c\u0131 olarak III akrilik re\u00e7ine kullanarak ART kat\u0131 dispersiyonu (ART-SD) ve s\u00fcrekli sal\u0131ml\u0131 ART-SD haz\u0131rlam\u0131\u015ft\u0131r. Tek bir ta\u015f\u0131y\u0131c\u0131 ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, iki veya daha fazla ta\u015f\u0131y\u0131c\u0131dan olu\u015fan karma bir ta\u015f\u0131y\u0131c\u0131 kullan\u0131larak kat\u0131 dispersiyonlar\u0131n haz\u0131rlanmas\u0131, ila\u00e7 sal\u0131m h\u0131z\u0131n\u0131 d\u00fczenlemede ve ila\u00e7 \u00e7\u00f6z\u00fcnmesini iyile\u015ftirmede daha fazla avantaja sahip olabilir. Bununla birlikte, ta\u015f\u0131y\u0131c\u0131 t\u00fcr\u00fcn\u00fcn ART'nin \u00e7\u00f6z\u00fcnmesi \u00fczerinde bir etkisi olup olmad\u0131\u011f\u0131 \u015fu anda belirsizdir ve ikili ta\u015f\u0131y\u0131c\u0131lar kullan\u0131larak h\u0131zl\u0131 sal\u0131ml\u0131 ART-SD haz\u0131rlamak i\u00e7in i\u015flem ko\u015fullar\u0131 optimize edilmemi\u015ftir. Bu makalede, kat\u0131 dispersiyonlar i\u00e7in yayg\u0131n olarak kullan\u0131lan bir ta\u015f\u0131y\u0131c\u0131 olan lesitin ve ikili ta\u015f\u0131y\u0131c\u0131 olarak PEG 6000 veya PVP K30 kullan\u0131larak farkl\u0131 ta\u015f\u0131y\u0131c\u0131 tiplerinin ve oranlar\u0131n\u0131n ila\u00e7 \u00e7\u00f6z\u00fcnmesi \u00fczerindeki etkileri kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. \u00c7ift ta\u015f\u0131y\u0131c\u0131l\u0131 h\u0131zl\u0131 sal\u0131ml\u0131 ART-SD'nin haz\u0131rlanma s\u00fcreci optimize edilmi\u015f ve optimum re\u00e7ete ile haz\u0131rlanan kat\u0131 dispersiyondaki ila\u00e7 ta\u015f\u0131y\u0131c\u0131lar\u0131n\u0131n var olma durumu IR ve DSC y\u00f6ntemleri ile a\u00e7\u0131kl\u0131\u011fa kavu\u015fturularak az \u00e7\u00f6z\u00fcnen ila\u00e7lar\u0131n klinik etkinli\u011finin iyile\u015ftirilmesi i\u00e7in \u00f6nemli bir temel at\u0131lm\u0131\u015ft\u0131r.<\/p>\n
Kat\u0131 dispersiyon teknolojisi, ila\u00e7lar\u0131 uygun ta\u015f\u0131y\u0131c\u0131 malzemeler i\u00e7inde y\u00fcksek oranda da\u011f\u0131t\u0131r ve amorf, mikrokristalin, molek\u00fcler dispersiyon veya kolloidal dispersiyon durumlar\u0131nda bulunur. Gastrointestinal s\u0131v\u0131larla temas ettikten sonra, ila\u00e7 \u00e7\u00f6z\u00fcnme h\u0131z\u0131 h\u0131zlan\u0131r, ila\u00e7 emilimini te\u015fvik eder ve biyoyararlan\u0131m\u0131 iyile\u015ftirir, b\u00f6ylece az \u00e7\u00f6z\u00fcn\u00fcr ila\u00e7lar\u0131n zay\u0131f oral emilimi sorununu iyile\u015ftirir. Ta\u015f\u0131y\u0131c\u0131n\u0131n \u00f6zelliklerine ve ila\u00e7 sal\u0131n\u0131m\u0131n\u0131n \u00f6zelliklerine g\u00f6re, kat\u0131 dispersiyonlar h\u0131zl\u0131 sal\u0131n\u0131m, kontroll\u00fc sal\u0131n\u0131m ve enterik kapl\u0131 kat\u0131 dispersiyonlar olarak ayr\u0131l\u0131r. Bu makalede, h\u0131zl\u0131 sal\u0131ml\u0131 ART-SD'de ART'nin h\u0131zl\u0131 sal\u0131m\u0131n\u0131 sa\u011flamak i\u00e7in hidrofilik ta\u015f\u0131y\u0131c\u0131 malzemeler se\u00e7ilmi\u015f ve iyi \u0131slatma \u00f6zelliklerinden yararlan\u0131lm\u0131\u015ft\u0131r. ART-SD'nin 50 dakika i\u00e7indeki \u00e7\u00f6z\u00fcnme oran\u0131, fiziksel kar\u0131\u015f\u0131mlardan ve ART hammaddelerinden \u00e7ok daha y\u00fcksektir ve bu da ART'nin oral uygulamas\u0131n\u0131n eksik emilimi sorununu \u00e7\u00f6zmek i\u00e7in faydal\u0131d\u0131r.<\/p>\n
\u0130kinci olarak, ikili ta\u015f\u0131y\u0131c\u0131lar ila\u00e7 \u00e7\u00f6z\u00fcnmesini tekli ta\u015f\u0131y\u0131c\u0131lardan daha b\u00fcy\u00fck \u00f6l\u00e7\u00fcde art\u0131rabilir. Soya lesitini \u00e7\u00f6z\u00fcn\u00fcrle\u015ftirme \u00f6zelliklerine sahipken, PVP K30 \u0131slanmay\u0131 art\u0131rma, \u00e7\u00f6z\u00fcnme ortam\u0131n\u0131n y\u00fczey gerilimini azaltma ve ila\u00e7 kristalizasyonunu engelleme \u00f6zelliklerine sahiptir. PVP K30, az \u00e7\u00f6z\u00fcnen ila\u00e7lar\u0131n \u00e7\u00f6z\u00fcnmesini iyile\u015ftirmek i\u00e7in yayg\u0131n olarak kullan\u0131lmaktad\u0131r. PEG 6000 ayr\u0131ca ART-SD'nin haz\u0131rlanmas\u0131 i\u00e7in ikili ta\u015f\u0131y\u0131c\u0131 olarak lesitin ile kar\u0131\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r, ancak farkl\u0131 kompozit ta\u015f\u0131y\u0131c\u0131lar\u0131n ART-SD'den ART'nin \u00e7\u00f6z\u00fcnmesi \u00fczerindeki etkisi \u015fu anda belirsizdir ve ikili ta\u015f\u0131y\u0131c\u0131lar kullan\u0131larak ART-SD'nin haz\u0131rlanmas\u0131 i\u00e7in i\u015flem ko\u015fullar\u0131 optimize edilmemi\u015ftir. Bu makale, ikili ta\u015f\u0131y\u0131c\u0131 olarak PVP K30 ve PEG 6000 ile kombine edilmi\u015f fosfatidilkolinin ART'nin \u00e7\u00f6z\u00fcnmesi \u00fczerindeki etkisini ara\u015ft\u0131rmaktad\u0131r. Fosfatidilkolin PVP K30'un daha \u00fcst\u00fcn oldu\u011fu bulunmu\u015f ve ikisinin oran\u0131 belirlenmi\u015ftir. Buna dayanarak, \u00e7ift ta\u015f\u0131y\u0131c\u0131l\u0131 \u00e7\u00f6z\u00fcc\u00fc y\u00f6ntemiyle h\u0131zl\u0131 sal\u0131ml\u0131 ART-SD haz\u0131rlamak i\u00e7in proses ko\u015fullar\u0131 optimize edilmi\u015f ve yeni ART form\u00fclasyonlar\u0131n\u0131n geli\u015ftirilmesi i\u00e7in \u00f6nemli bir temel at\u0131lm\u0131\u015ft\u0131r.<\/p>\n
Bu deneyde, ART'nin \u00e7\u00f6z\u00fcnme h\u0131z\u0131 de\u011ferlendirme indeksi olarak kullan\u0131lm\u0131\u015ft\u0131r. \u0130kili ta\u015f\u0131y\u0131c\u0131 tipleri, kompozit ta\u015f\u0131y\u0131c\u0131 oranlar\u0131, reaksiyon s\u00fcresi, \u00e7\u00f6z\u00fcc\u00fc dozaj\u0131 vb. tek fakt\u00f6rl\u00fc taramayla, ikili ta\u015f\u0131y\u0131c\u0131 sistem kullan\u0131larak h\u0131zl\u0131 sal\u0131ml\u0131 ART-SD haz\u0131rlamak i\u00e7in en uygun form\u00fclasyon \u015fu \u015fekilde belirlenmi\u015ftir: 50 mg ART, 50 mg soya lesitini, 350 mg PVP K30 (soya lesitini ve PVP K30 oran\u0131 1:7). Optimal prosesle haz\u0131rlanan kat\u0131 dispersiyondaki ila\u00e7 i\u00e7eri\u011fi 10.55% \u00b1 0.04% olup 30 dakikada \u00e7\u00f6z\u00fcnme dengesine ula\u015fm\u0131\u015ft\u0131r. \u00c7\u00f6z\u00fcnme h\u0131z\u0131 50 dakika i\u00e7inde 87.21% \u00b1 2.28% olup PM 3.45% \u00b1 1.68% ve ART hammaddesinden 0.05% \u00b1 0.15% \u00f6nemli \u00f6l\u00e7\u00fcde daha y\u00fcksektir. DSC ve IR analizleri, ART ile ta\u015f\u0131y\u0131c\u0131 aras\u0131nda hidrojen ba\u011flar\u0131n\u0131n olu\u015ftu\u011funu ve yeni bir amorf halde bulundu\u011funu g\u00f6stermektedir. ART-SD'nin az \u00e7\u00f6z\u00fcnen bir ila\u00e7 olarak ART'nin d\u00fc\u015f\u00fck oral biyoyararlan\u0131m\u0131n\u0131 iyile\u015ftirip iyile\u015ftiremeyece\u011fini, anti s\u0131tma aktivitesini art\u0131r\u0131p art\u0131ramayaca\u011f\u0131n\u0131 ve klinik kullan\u0131m i\u00e7in daha etkili anti s\u0131tma ila\u00e7lar\u0131 sa\u011flay\u0131p sa\u011flayamayaca\u011f\u0131n\u0131 belirlemek i\u00e7in daha fazla ara\u015ft\u0131rma yap\u0131lacakt\u0131r.<\/p>","protected":false},"excerpt":{"rendered":"
\u00c7ift ta\u015f\u0131y\u0131c\u0131 sistem kullan\u0131larak artemisinin h\u0131zl\u0131 sal\u0131n\u0131ml\u0131 kat\u0131 dispersiyon haz\u0131rlama s\u00fcrecinin optimizasyonu S\u0131tma, s\u0131tma parazitlerinin neden oldu\u011fu, sivrisinekler taraf\u0131ndan bula\u015ft\u0131r\u0131lan ve d\u00fcnya \u00e7ap\u0131nda yayg\u0131n olarak g\u00f6r\u00fclen olduk\u00e7a \u00f6l\u00fcmc\u00fcl k\u00f6t\u00fc huylu bula\u015f\u0131c\u0131 bir hastal\u0131kt\u0131r. S\u0131tma parazitlerinin d\u00f6ng\u00fcsel bula\u015fmas\u0131 ve karma\u015f\u0131k ya\u015fam d\u00f6ng\u00fcs\u00fc, s\u0131tman\u0131n tamamen ortadan kald\u0131r\u0131lmas\u0131n\u0131 zorla\u015ft\u0131rm\u0131\u015ft\u0131r. Geleneksel antimalaryal ila\u00e7lar\u0131n \u00e7o\u011fu, \u00f6rne\u011fin [...]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"\n