Publication: Düşük çözünürlüklü ilaç etken maddelerinin misellerle çözündürülmesi
Abstract
Bu çalışmada suda sınırlı çözünürlüğü olan, az çözünen veya hiç çözünmeyen ilaç etken maddelerinden Clopidogrel bisulfate, Ganciclovir sodium, Miconazole nitrate, Brinzolamide, Brimonidine tartarate, Dexamethasone’nın farklı yapıdaki anyonik; sodyumdodesil sülfat (SDS) ve aeresol-OT (AOT) ve katyonik; dodesiltrimetilamonyum bromür (DTAB) ve setiltrimetilamonyum bromür (CTAB) yüzey aktif madde (YAM) miselleri ile çözündürülmesi ve çözündürme mekanizmasının aydınlatılması amaçlandı. İlaç etken maddelerinin YAM miselleri ile çözündürme çalışmaları spektroskopik ölçümlerle yürütüldü. Higuchi-Connars yöntemi kullanılarak faz-çözünürlük grafikleri oluşturuldu ve elde edilen faz çözünürlük grafikleri yardımıyla misellerin çözündürme etkinliği incelendi. Model olarak seçilen, anyonik SDS ve AOT ve katyonik DTAB ve CTAB miselleri, ile çözündürme model çalışması niteliği taşıyan bu çalışmada, Clopidogrel bisulfate (suda çözünmez), Ganciclovir sodium (suda çözünür), Miconazole nitrate (suda sınırlı çözünür), Brinzolamide (suda çözünmez), Brimonidine tartarate (suda sınırlı çözünür), Dexamethasone (suda çözünmez) İEM’lerinin çalışılan misellerle çözündürülme etkinlikleri karşılaştırıldı. Faz çözünürlük grafiklerinden elde edilen doğruların yardımıyla YAM misellerinin çözündürme kapasiteleri (Km) hesaplandı. YAM miselleri İEM’lerinin çözündürülmesine katkı sağladı. YAM’lerin hidrofobikliğinin artması ile çözündürmenin gücünün özellikle suda çözünmeyen veya az çözünen etken maddeler için olumlu yönde arttığı görüldü. YAM’lerin etkinlik derecesi anyonikler için AOT>SDS katyonikler için ise CTAB>DTAB sırasını izledi. Çalışılan misel sistemleri içerisinde en etkili YAM’nin AOT olduğu tespit edildi.
The aim of this study is solubilization of Clopidogrel bisulfate, Ganciclovir sodium, Miconazole nitrate, Brinzolamide, Brimonidine tartarate, Dexamethasone, which are limited soluble, slightly soluble or insoluble drugs in water by anionics sodiumdodecyl sulfate (SDS) and aerosol-OT (AOT) and cationics dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB) micelles at 298 K and elucidate of their solubilization mechanism. Solubilization studies of drugs with surfactant micelles were carried out with spectroscopic measurements. Phase-solubilization graphs were plotted using the Higuchi-Connars method. The solubilization efficiency of the micelles was examined with the help of the obtained phase solubilization graphs. The solubilization efficiencies of CTAB, DTAB, SDS and AOT micelles which were selected as a model for Clopidogrel bisulfate (insoluble in water), Ganciclovir sodium (soluble in water), Miconazole nitrate (limited soluble in water), Brinzolamide (insoluble in water), Brimonidine tartarate (slightly soluble in water), Dexamethasone (insoluble in water) were compared. With the help of slopes obtained from the phase solubilization graphs, the solubilization capacities (Km) of the surfactant micelles were calculated. Surfactant micelles used in this study contributed to the solubilization of drugs. It was observed that with the increase of hydrophobicity of surfactants, the solubilization efficiency increased, especially for water-insoluble or slightly soluble drugs. The degree of solubilization ability of micelles followed the order as AOT>SDS for anionics and CTAB>DTAB for cationics. However, it was determined that the most effective surfactant among the studied micelle systems was AOT.
The aim of this study is solubilization of Clopidogrel bisulfate, Ganciclovir sodium, Miconazole nitrate, Brinzolamide, Brimonidine tartarate, Dexamethasone, which are limited soluble, slightly soluble or insoluble drugs in water by anionics sodiumdodecyl sulfate (SDS) and aerosol-OT (AOT) and cationics dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB) micelles at 298 K and elucidate of their solubilization mechanism. Solubilization studies of drugs with surfactant micelles were carried out with spectroscopic measurements. Phase-solubilization graphs were plotted using the Higuchi-Connars method. The solubilization efficiency of the micelles was examined with the help of the obtained phase solubilization graphs. The solubilization efficiencies of CTAB, DTAB, SDS and AOT micelles which were selected as a model for Clopidogrel bisulfate (insoluble in water), Ganciclovir sodium (soluble in water), Miconazole nitrate (limited soluble in water), Brinzolamide (insoluble in water), Brimonidine tartarate (slightly soluble in water), Dexamethasone (insoluble in water) were compared. With the help of slopes obtained from the phase solubilization graphs, the solubilization capacities (Km) of the surfactant micelles were calculated. Surfactant micelles used in this study contributed to the solubilization of drugs. It was observed that with the increase of hydrophobicity of surfactants, the solubilization efficiency increased, especially for water-insoluble or slightly soluble drugs. The degree of solubilization ability of micelles followed the order as AOT>SDS for anionics and CTAB>DTAB for cationics. However, it was determined that the most effective surfactant among the studied micelle systems was AOT.