ORAL RİTONAVİR AMORF KATI DİSPERSİYONLARININ YİYECEK ETKİSİNİ TAHMİN ETMEK İÇİN BİYOUYUMLU ORTAMLARIN DEĞERLENDİRİLMESİ

Öz

Amaç: Polimerlerin, biyouyumlu ortamlarda filmlerin çözünürlüğü, çözünme kapasitesi ve çözünmesi üzerindeki etkilerinin değerlendirilmesi ve böylece yiyeceklerin RTN üzerindeki olumsuz etkisinin altında yatan temel mekanizmanın anlaşılması amaçlanmıştır. Gereç ve Yöntem: Çeşitli polimerlerle çözücü-dökme yöntemi ile amorf filmler hazırlanmıştır, daha sonra biyouyumlu ortamlarda (FeSSIF-V2 ve FaSSIF-V2) ve maleik asit tamponlarında (pH 5.8 ve 6.5) çözünürlük, çözünme kapasitesi ve çözünme hızı çalışmaları gerçekleştirilmiştir. Sonuç ve Tartışma: FeSSIF-V2'de RTN çözünürlüğünü artırmak için polimer sıralaması SoluPlus>Eudragit S100>PVPVA=PEG6000>HPMCAS-L’dir. FaSSIF-V2 için sadece Eudragit S100, SoluPlus ve PVPVA RTN çözünürlüğünü artırmıştır. Çözünürlük kapasitesi çalışmaları, RTN salınımının FeSSIF-V2'de HPMCAS-H hariç ve FaSSIF-V2'de HPMCAS-H ve HPMCAS-L:H hariç tüm polimerler için %20 ilaç yüklemeye sahip filmlerde %40'tan daha yüksek olduğunu göstermiştir. FeSSIF-V2'de çözünme çalışmaları, HPMCAS-L ve PVPVA'dan elde edilen RTN filmlerinin erken zaman noktalarında diğer polimerlere kıyasla daha yüksek RTN salınımı sağladığını göstermiştir. FaSSIF-V2 ortamındaki AUC(0-120 dk) sırasıyla SoluPlus, HPMCAS-L, PVPVA ve HPMCAS-L:H için kristal RTN ile karşılaştırıldığında 9.0 kat, 8.3 kat, 5.9 kat ve 5.0 kat daha yüksek bulunmuştur. Bununla birlikte, bu çalışmada in vitro olarak görülmeyen RTN'nin negatif yiyecek etkisi, burada FeSSIF-V2 ve FaSSIF-V2 kullanılarak simüle edilenden daha karmaşık ilaç, polimer ve yiyecek etkileşimlerinden kaynaklanıyor olabilir.

Anahtar Kelimeler

• Biouyumlu ortam
• film
• ritonavir
• yiyecek etkisi

ASSESSMENT OF BIORELEVANT MEDIA TO ANTICIPATE FOOD EFFECT OF ORAL RITONAVIR AMORPHOUS SOLID DISPERSIONS

Öz

Objective: The objective was to evaluate the polymers effects on solubility, solubilization capacity and dissolution of films in biorelevant media, thus, to understand the main mechanism underlaying RTN’s negative food effect. Material and Method: Amorphous films were prepared with various polymers via solvent-casting method, then solubility, solubilization capacity and dissolution studies were performed in biorelevant media (FeSSIF-V2 and FaSSIF-V2) and maleic acid buffers (pH 5.8 and 6.5). Result and Discussion: Polymer rank-order to increase RTN solubility in FeSSIF-V2 was SoluPlus>EudragitS100>PVPVA=PEG6000>HPMCAS-L. For FaSSIF-V2, only EudragitS100, SoluPlus and PVP-VA increased RTN solubility. Solubilization capacity studies showed that RTN release was higher for 20% drug loaded films than for 40% for all polymers except for HPMCAS H in FeSSIF-V2, and for HPMCAS-H and HPMCAS-L:H in FaSSIF-V2. In FeSSIF-V2, dissolution studies showed that RTN films from HPMCAS-L and PVP-VA provided higher RTN release compared to other polymers in early time points. AUC(0-120 min) in FaSSIF-V2 media was 9.0-fold, 8.3-fold, 5.9-fold, and 5.0-fold higher for SoluPlus, HPMCAS-L, PVPVA and HPMCAS-L:H, respectively, compared to crystalline RTN. Although, RTN’s negative food effect, which was not replicated here in vitro, may be due to more complex interactions between drug, polymer, and food in vivo than simulated here using FeSSIF-V2 and FaSSIF-V2.

Anahtar Kelimeler

• Biorelevant media
• film
• food effect
• ritonavir

Kaynakça

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