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

Year 2024, , 867 - 875, 10.09.2024

Tansel Çomoğlu

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

Abstract

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.

Keywords

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

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

Abstract

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.

Keywords

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

References

• 1. Yoo, S.D., Lee, S., Kang, E., Jun, H., Jung, J., Park, J.W., Lee, K. (2000). Bioavailability of itraconazole in rats and rabbits after administration of tablets containing solid dispersion particles. Drug Development and Industrial Pharmacy, 26(1), 27-34. [CrossRef]
• 2. Rouf, M.A., Vural, İ., Bilensoy, E., Hıncal, A.A., Erol, D. (2010). Rapamycin-cyclodextrin complexation: Improved solubility and dissolution rate. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 70(1-2), 167-175. [CrossRef]
• 3. Gökbulut, E., Özdemir, N., (2017). Enhancement of solubility of itraconazole by complexation with ß cyclodextrin derivatives. Fabad Journal of Pharmaceutical Sciences, 42(1), 1-6.
• 4. Çomoğlu, T., Özyilmaz, E.D. (2019). Orally disintegrating tablets and orally disintegrating mini tablets-novel dosage forms for pediatric use. Pharmaceutical Development and Technology, 24(7), 902-914. [CrossRef]
• 5. Yin, X., Daintree, L.S., Ding, S.L., Ledger, D.M., Wang, B., Zhao, W., Qi, J., Wu, W. (2015). Itraconazole solid dispersion prepared by a supercritical fluid technique: Preparation, in vitro characterization, and bioavailability in beagle dogs. Drug Design Development and Therapy, 2015, 2801-2810. [CrossRef]
• 6. Shaheen, N., Zaman, S.U. (2018). Development of fast dissolving tablets of flurbiprofen by sublimation method and its in vitro evaluation. Brazilian Journal of Pharmaceutical Sciences, 54(4), e17061. [CrossRef]
• 7. Özyılmaz, E.D., Çomoğlu, T. (2023). Evaluation of two different orally disintegrating tablet formulations containing flurbiprofen inclusion complex and its solid dispersion. Tropical Journal of Pharmaceutical Research (Online), 22(4), 705-711. [CrossRef]
• 8. Nijhu, R.S., Khatun, A., Hossen, M.F. (2024). A comprehensive review of particle size analysis techniques. International Journal of Pharmaceutical Research and Development, 6(1), 01-05. [CrossRef]
• 9. Vemula, S.K., Neduri, K. (2015). Lovastatin fast dissolving tablets: Formulation and in vitro evaluation. Applied Science Reports, 11(2), 76-82. [CrossRef]
• 10. Mishra, D.N., Bindal, M., Singh, S.K., Kumar, S.G.V. (2006). Spray dried excipient base: A novel technique for the formulation of orally disintegrating tablets. Chemical & Pharmaceutical Bulletin, 54(1), 99-102. [CrossRef]
• 11. Khinchi, M.P., Gupta, M.K., Bhandari, A., Sharma, N., Agarwal, D. (2011). Design and development of orally disintegrating tablets of famotidine prepared by direct compression method using different superdisintegrants. Journal of Applied Pharmaceutical Science, 1(1), 50-58.
• 12. Brniak, W., Jachowicz, R., Pelka, P. (2015). The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs). Saudi Pharmaceutical Journal, 23(4), 437-443. [CrossRef]
• 13. Devi, M.S., Saraswathi, L., Chitraksh, A.S., Ch, M., Sairaj, M., Tajudin, S., Aishwarya, C. (2023). A study on evaluate pre-compression and post compression parameters of the formulated tablets using folic acid. European Chemical Bulletin, 12(5), 6356-6363.
• 14. Miyake, K., Irie, T., Arima, H., Hirayama, F., Uekama, K., Hirano, M., Okamoto, Y. (1999). Characterization of itraconazole/2-hydroxypropyl-β-cyclodextrin inclusion complex in aqueous propylene glycol solution. International Journal of Pharmaceutics, 179(2), 237-245. [CrossRef]
• 15. Hassan, H.A., Al‐Marzouqi, A.H., Jobe, B., Hamza, A.A., Ramadan, G.A. (2007). Enhancement of dissolution amount and in vivo bioavailability of itraconazole by complexation with β-cyclodextrin using supercritical carbon dioxide. Journal of Pharmaceutical and Biomedical Analysis, 45(2), 243-250. [CrossRef]
• 16. Badawi, A., El-Nabarawi, M.A., El-Setouhy, D.A., Alsammit, S.A. (2011). Formulation and stability testing of itraconazole crystalline nanoparticles. AAPS PharmSciTech, 12(3), 811-820. [CrossRef]