VALSARTAN İÇEREN KATI VE SIVI KENDİLİĞİNDEN EMÜLSİFİYE OLAN SİSTEMLER (SEDDS): STABİLİTE DEĞERLENDİRMESİ VE PERMEABİLİTE ÇALIŞMALARI

Öz

Amaç: Valsartan (VST), biyoyararlanımı yaklaşık %25 olan Biyofarmasötik Sınıflandırma Sistemi (BSS) sınıf II aktif maddedir ve yüksek kan basıncını (hipertansiyon) tedavi etmek için kullanılır. Bu çalışmanın amacı, kendi kendine emülsifiye olan ilaç dağıtım sistemleri (SEDDS) ve katılaştırılmış SEDDS (S-SEDDS) formülasyonları geliştirerek VST'nin stabilitesini göstermek ve geçirgenliğini artırmaktır. Gereç ve Yöntem: Bir önceki çalışmada bileşenlerin oranları üçgen faz diyagramı ile belirlenmiş olup, karakterizasyon çalışmaları yapılmıştır. Bu çalışmada, uzun süreli (25±2˚C, 60±5% bağıl nem) ve hızlandırılmış (40±2˚C, 75±5% bağıl nem) koşullarda stabilite çalışmaları gerçekleştirildi. SEDDS formülasyonlarının bağırsak geçirgenliği Caco-2 hücreleri tarafından değerlendirildi. Sonuç ve Tartışma: Formülasyonların 12 ay boyunca partikül boyutları VST içeren SEDDS (VST-SEDDS) formülasyuonunda 67.52 ± 5.26 nm, VST içeren S-SEDDS (VST-S-SEDDS) formülasyonunda 176.93 ± 17.34 nm olarak bulundu. Bu süre boyunca VST-SEDDS ve VST-S-SEDDS formülasyonunun polidispersite indeksleri sırasıyla 0.56±0.1, 0.58±0.05 olarak bulundu. Her iki formülasyon da Caco-2 hücreleri boyunca VST geçirgenliğini artırdı: VST-SEDDS 2,32 kat (toz) ve 2,18 kat (ticari); VST-S-SEDDS 1,38x (toz) ve 1,30x (ticari). Formülasyonların bileşenlerinde sitotoksik etki görülmedi. Bu sonuçlar, yüksek geçirgenliğe sahip yeni geliştirilen VST-SEDDS ve VST-S-SEDDS formülasyonlarının antihipertansif tedavi için arzu edilen bir yaklaşım olabileceğini gösterdi.

Anahtar Kelimeler

• Caco-2 hücre hattı
• kendi kendine emülsifiye olan ilaç dağıtım sistemleri
• katılaştırılmış kendi kendine emülsifiye olan ilaç dağıtım sistemleri
• permeabilite
• valsartan

LIQUID AND SOLID SELF-EMULSIFYING DRUG DELIVERY SYSTEMS (SEDDS) CONTAINING VALSARTAN: STABILITY ASSESSMENT AND PERMEABILITY STUDIES

Öz

Objective: Valsartan (VST) is a Biopharmaceutical classification system (BSC) class II active ingredient with a bioavailability of approximately 25% and is utilized to treat high blood pressure (hypertension). This study aimed was to showcase the stability and increase the permeability of VST by developing self-emulsifying drug delivery systems (SEDDS) and solidified SEDDS (S-SEDDS) formulations. Material and Method: The ratios of the components were determined by the pseudo-ternary phase diagram, and the characterization studies were conducted in the previous study. Stability was performed in long-term (25±2˚C, 60±5% relative humidity) and accelerated (40±2˚C, 75±5% relative humidity) conditions. The intestinal permeability of SEDDS formulations was evaluated by Caco-2 cells. Result and Discussion: Formulations for 12 month, droplet sizes were found to be 67.52 ± 5.26 nm and 176.93 ± 17.34 nm for SEDDS of VST (VST-SEDDS) and S-SEDDS of VST (VST-S-SEDDS), respectively. During this period, polydispersity indexes were: VST-SEDDS, 0.56±0.1; VST-S-SEDDS, 0.58±0.05. Both formulations increased VST permeability across Caco-2 cells: VST-SEDDS by 2.32x (powder) and 2.18x (commercial); VST-S-SEDDS by 1.38x (powder) and 1.30x (commercial). The formulation components did not have cytotoxic effects. These results demonstrated that newly developed VST-SEDDS and VST-S-SEDDS formulations with high permeability may be a desirable approach for antihypertensive therapy.

Anahtar Kelimeler

• Caco-2 cell line
• permeability
• self-emulsifying drug delivery system
• solidified self-emulsifying drug delivery system
• valsartan

Kaynakça

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