İNDOMETAZİN İÇEREN OKÜLER İN SİTU JEL FORMÜLASYONU GELİŞTİRİLMESİ VE KARAKTERİZASYONU

Öz

Amaç: Bu çalışma, oküler inflamatuar hastalıkların etkin tedavisi için kornea yüzeyinde İndometazin’in (INDO) kalış süresini uzatarak oküler biyoyararlanımını artıracak in-situ jel formülasyonları hazırlamayı amaçlamaktadır. Gereç ve Yöntem: Formülasyonlar, soğukta hazırlama yöntemi ile hazırlanmıştır. Bu yöntemde kısaca polimerler soğutulmuş distile suda çözündürülerek INDO eklenmiş ve homojen hale getirilmiştir. Analitik çalışmalarda düzenlenmiş bir UV yöntemi kullanılmıştır. INDO ve yardımcı maddelerin yapısal özelliklerinin belirlenmesi adına DSC, FT-IR ve ¹H-NMR analizleri kullanılmıştır. Formülasyonların karakteristik özellikleri; jelleşme sıcaklığı ve jelleşme süresi, pH, reolojik analizler ve in vitro salım çalışmaları (pH 7.4 PBS, 34 ± 2°C) ile değerlendirilmiştir. Sonuç ve Tartışma: Jelleşme sıcaklığı ve jelleşme süresi analizlerine göre, %17 (a/a) Poloksamer 407 (P407) içeren optimal formülasyon daha sonraki çalışmalar için seçilmiştir. Etkin madde-polimer geçimliliği DSC, FT-IR ve ¹H-NMR analizleri ile doğrulanmıştır. INDO, formülasyona %0.1 (a/a) oranında yüklenmiştir. Formülasyonun pH değeri 5.29 ± 0.00 olarak belirlenmiş ve oküler tolerans göz önünde bulundurularak herhangi bir pH ayarlamasına gerek duyulmamıştır. Reolojik analizler, jelleşme noktasının 34 ± 2°C olduğunu ortaya koymuştur. In vitro salım analizleri, 6 saat sonunda INDO’nun yalnızca %30’unun salındığını göstermiştir. Bu durum, göz damlasının jel yapıya dönüşmesi sayesinde etkin maddenin uzamış salımını ortaya koymaktadır. Bu sonuçlar, INDO’nun kornea yüzeyinde uzamış kalış süresi dikkate alındığında, P407 bazlı in situ jellerle oküler biyoyararlanımın artırılacağı düşüncesini desteklemektedir.

Anahtar Kelimeler

• İndometazin
• in-situ jel
• oküler inflamasyon
• poloksamer 407

DEVELOPMENT AND CHARACTERIZATION OF AN OCULAR IN SITU GEL FORMULATION CONTAINING INDOMETHACIN

Öz

Objective: This study aims to formulate in-situ gel formulations for extended duration of indomethacin (INDO) on the corneal surface which will improve the ocular bioavailability for sufficial treatment of ocular inflammatory disorders. Material and Method: Formulations were prepared by cold method. Briefly polymers were dissolved in cold ultrapure water and INDO was added to the solutions. A modified UV method was used. DSC, FT-IR and 1H-NMR analyses were used for the determination of structural properties of INDO and excipients. The formulations were characterized through measurements of gelation temperature and gelation time, determination of pH, rheological assessments, and in vitro drug release experiments conducted in PBS (pH 7.4) at 34 ± 2°C. Result and Discussion: According to the gelation temperature and gelation time analyses optimum formulation which contained %17 (w/w) Poloxamer 407 (P407) was selected for further studies. Evidence of drug–polymer compatibility was obtained through DSC, FT-IR, and ¹H-NMR studies. INDO was loaded to the formulation at 0.1% (w/w). pH of the formulation was 5.29±0.00 and considering the ocular tolerability no adjustment was required. The rheological analyses revealed the gel transition point at 34°C±2°C. In vitro release analyses revealed that even after 6 hours only 30% of the INDO was released from the formulations showing the extended release of the active agent with the help of transition of the eye drops to the solidified gel structure. These results support the notion that ocular bioavailability will be enhanced with P407 based in-situ gels considering extended retention time of INDO on the corneal surface.

Anahtar Kelimeler

• Indomethacin
• in situ gel
• ocular inflammation
• poloxamer 407

Kaynakça

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