2-hidroksipropil-β-siklodekstrin ile Metronidazolün İnklüzyon Kompleksi Oluşumunun HPLC Yöntemi ile Belirlenmesi

Abstract

Metronidazol, bakteri, protozoa ve parazitlerin neden olduğu enfeksiyonları tedavi etmek için kullanılan nitroimidazol sınıfı bir antibiyotiktir. Aktif farmasötik bileşenin düşük çözünürlüğü, ilaç absorpsiyonu ve biyoyararlanımı üzerindeki olumsuz etkisinden dolayı oral katı dozaj formlarının geliştirilmesi ve büyük ölçekli üretiminin önündeki en büyük engeldir. Bu çalışmada lipofilik yapıya sahip ve suda çözünürlüğü düşük olan metronidazolün çözünürlüğünü ve stabilitesini arttırmak için 2-hidroksipropil-β-siklodekstrin ile inklüzyon kompleksi oluşumu gerçekleştirilmiştir. 2-hidroksipropil-β-siklodekstrinin metronidazolün çözünürlüğü üzerindeki etkisi, faz çözünürlük metoduna göre değerlendirilmiştir. Metronidazolün 2-hidroksipropil-β-siklodekstrin ile kompleksleşmesi yüksek performans sıvı kromatografisi yöntemi ile belirlenmiştir. Sıvı kromatografik tayin, 25oC'de Kinetex Core-Shell C8 (Phenomenex, 150 x 4,6 mm I.D., 2,6 µm) kolonu ile gerçekleştirilmiştir. Mobil faz olarak %30 (h/h) asetonitril içeren asetonitril-su ikili karışımı kullanılmıştır. Sonuç olarak kompleksin stokiyometrisi 1:1’dir ve kompleksin kararlılık sabiti yüksek performans sıvı kromatografisi yöntemi ile belirlenmiştir.

Keywords

• Metronidazol
• İnklüzyon kompleksi
• Faz çözünürlük metodu
• HPLC

Determination of Inclusion Complex Formation of Metronidazole with 2-Hydroxypropyl-β-Cyclodextrin by HPLC Method

Abstract

Metronidazole is a nitroimidazole class antibiotic used to treat infections caused by bacteria, protozoa, and parasites. The low solubility of the active pharmaceutical ingredient is the major obstacle to the development and large-scale production of oral solid dosage forms due to its adverse effect on drug absorption and bioavailability. In this study, inclusion complex formation was carried out with 2-hydroxypropyl-β-cyclodextrin to increase the solubility and stability of metronidazole, which has a lipophilic structure and low water solubility. The influence of 2-hydroxypropyl-β-cyclodextrin on the metronidazole solubility was evaluated in respect of the phase solubility method. The complexation of metronidazole with 2-hydroxypropyl-β-cyclodextrin was proven by high performance liquid chromatography method. Liquid chromatographic determination was carried out on a Kinetex Core-Shell C8 (Phenomenex, 150 x 4.6 mm I.D., 2.6 μm) column at 25oC. The acetonitrile-water binary mixture containing 30% (v/v) acetonitrile was used as a mobile phase. As a result, the stoichiometry of the complex was 1:1 and the stability constant of the complex was determined by the high performance liquid chromatography method.

Keywords

• Metronidazole
• Inclusion complex
• Phase solubility method
• HPLC

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