Tamoksifen Sitrat Yüklü Ɣ-Sİklodekstrin Metal Organik Çerçevelerinin Geliştirilmesi ve Karakterizasyonu

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Mutlu Ağardan N. B., Edisan Ş.

4th International Symposium on Pharmaceutical Sciences (ISOPS), Ankara, Türkiye, 25 - 28 Haziran 2024, ss.264

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Ankara
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.264
  • Gazi Üniversitesi Adresli: Evet

Özet

DEVELOPMENT AND CHARACTERIZATION OF TAMOXIFEN CITRATE LOADED ɣ-CYCLODEXTRIN METAL ORGANIC FRAMEWORKS

1Mutlu Ağardan, NB, 1Edisan Ş.

1 Gazi University, Department of Pharmaceutical Technology, Ankara, Turkey,

bmutlu@gazi.edu.tr, seymaaydogduoglu@gazi.edu.tr

 

Introduction:ɣ-Cyclodextrin metal-organic frameworks (ɣ-CD-MOFs) are novel drug delivery systems prepared with gamma-cyclodextrin and alkali metal cations which constitute a class of porous, edible nanomaterials with high surface area (1). Tamoxifen citrate is widely used for preventing recurrence of ER-positive breast cancers (2,3). It is a BCS II drug, a weak base, characterized with rapid dissolution in the gastric environment with possible precipitation expected due to the high pH in the duodenum (4). In this study, it was aimed to increase the solubility of TMX by preparing TMX-ɣ-CD-MOF formulations and fully characterize the TMX-ɣ-CD-MOFs.

Materials and Methods:Two different ɣ-CD-MOF were prepared by modified methanol diffusion method with slight modifications. Tamoxifen was encapsulated in ɣ-CD-MOFs via impregnation method at 60°C. Loading efficiency was measured by UV spectrophotometry at 235 nm. Characterization studies were carried out using DLS, SEM, DSC, XRD, BET techniques. Solubility studies were performed with TMX-ɣ-CD-MOFs comparatively with pure drug and physical mixture (1:1) in pH 1.2, pH 4.5 and pH 6.8 at 37°C and in water at 25°C.

Results:The formulations were prepared by two methods were named TMX-ɣ-CD-MOF-1 and TMX-ɣ-CD-MOF-2 with particle sizes 606,3±38,40 nm and 337,8±31,86 nm, respectively. The solubility of TMX was successfully increased in pH 1.2, pH 4.5, pH 6.8 and water with ɣ-CD-MOF formulations. TMX-ɣ-CD-MOF-2 found to be more successful in enhancing solubility of TMX,considered to be a result of its lower particle size.

Conclusions: ɣ-Cyclodextrin metal-organic frameworks(ɣ-CD-MOFs) are promising novel drug delivery systems to enhance solubility hence dissolution rate of BCS II and IV drugs.

Acknowledgments

This study was supported by a grant of TÜBİTAK(SBAG-222S923). Şeyma Edisan thanks for financial support from TÜBITAK(BIDEB/2211-A).

References:

1.Han, Y., Liu, W., Huang, J., Qiu, S., Zhong, H., Liu, D., & Liu, J. (2018). Cyclodextrin-Based Metal-Organic Frameworks (CD-MOFs) in Pharmaceutics and Biomedicine. Pharmaceutics, 10(4), 271.

2. Manna S, Holz MK. Tamoxifen Action in ER-Negative Breast Cancer. Sign Transduct Insights. 2016 Feb 10;5:1-7.

3.Ravikumara NR, Bharadwaj M, Madhusudhan B. Tamoxifen citrate-loaded poly(d,l) lactic acid nanoparticles: Evaluation for their anticancer activity in vitro and in vivo. J Biomater Appl. 2016 Nov;31(5):755-772.

4. Ağardan, N. M., Değim, Z., Yılmaz, Ş., Altıntaş, L., & Topal, T. (2020). Tamoxifen/raloxifene loaded liposomes for oral treatment of breast cancer. Journal of Drug Delivery Science and Technology, 57, 101612.