ENHANCING SOLUBILITY AND DEVELOPING AN ITRACONAZOLE-BETA-CYCLODEXTRIN COMPLEX FOR ANTIFUNGAL THERAPY IN ORALLY DISINTEGRATING TABLETS

Yıl 2024, , 867 - 875, 10.09.2024

Tansel Çomoğlu

https://doi.org/10.33483/jfpau.1465360

Öz

Objective: This study aimed to create an orally disintegrating tablet (ODT) formulation using an itraconazole (ITZ)-beta-cyclodextrin (β-CD) complex to enhance itraconazole's solubility, a drug with limited solubility. β-CD was chosen for its compatibility with ITZ.
Material and Method: The study prepared equimolar mixtures of ITZ and β-CD through kneading, assessing their solubility and dissolution rates. The inclusion complexes significantly increased ITZ's solubility. This complex was used to develop directly compressed ODTs with a lower ITZ content (25 mg), incorporating D-Mannitol as a bulking agent, sweetener, and to enhance mouthfeel, facilitating rapid disintegration and drug release.
Result and Discussion: ODT formulations containing the ITZ-β-CD complex showed a significantly higher dissolution rate of ITZ compared to formulations with pure ITZ. This enhancement in dissolution is expected to significantly improve ITZ's bioavailability, suggesting a potential for reducing ITZ dosage and minimizing adverse effects.

Anahtar Kelimeler

β-cyclodextrin, complexation, itraconazole, kneading method, orally disintegrating tablet

AĞIZDA DAĞILAN TABLETLERDE ANTİFUNGAL TEDAVİ İÇİN ÇÖZÜNÜRLÜĞÜN ARTIRILMASI VE İTRAKONAZOL-BETA-SİKLODEKSTRİN KOMPLEKSİNİN GELİŞTİRİLMESİ

Öz

Amaç: Bu çalışma, sınırlı çözünürlüğe sahip itrakonazolün (ITZ) hızlı ve tam çözünürlüğünü sağlamak üzere ITZ-beta-siklodekstrin (β-CD) kompleksi kullanarak oral olarak dağılan bir tablet (ODT) formülasyonu geliştirmeyi hedeflemiştir. ITZ ile uyumluluğu nedeniyle β-CD tercih edilmiştir.
Gereç ve Yöntem: İtrakonazol ve β-CD'nin ekimolar karışımları yoğurma yöntemiyle hazırlanmış, çözünürlük ve çözünme oranları değerlendirilmiştir. İnklüzyon kompleksleri sayesinde ITZ'nin çözünürlüğünde önemli bir artış sağlanmıştır. Bu kompleksler kullanılarak, daha düşük ITZ içeriği (25 mg) ile doğrudan basılan ODT'ler geliştirilmiştir. D-Mannitol, hacim arttırıcı, tatlandırıcı olarak kullanılmış ve ağızda hızlı dağılma sağlamıştır.
Sonuç ve Tartışma: ITZ-β-CD kompleksini içeren ODT formülasyonları, saf ITZ içerenlere göre daha yüksek çözünmüş ilaç miktarı sergilemiştir. Bu, itrakonazolün çözünürlüğünde ve biyoyararlanımında önemli bir artış sağlamış, ITZ dozajının azaltılması ve yan etkilerin minimize edilmesi potansiyelini ortaya koymuştur.

Anahtar Kelimeler

Ağızda hızlı çözünen tablet, β-siklodekstrin, itrakonazol, kompleksleştirme, örme yöntemi

Kaynakça

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