Research in Pharmaceutical Sciences

ORIGINAL ARTICLE
Year
: 2022  |  Volume : 17  |  Issue : 4  |  Page : 334--349

Weak complexation of 5-fluorouracil with β-cyclodextrin, carbonate, and dianhydride crosslinked β-cyclodextrin: in vitro and in silico studies


Hadeia Mashaqbeh1, Rana Obaidat1, Nizar A Al-Shar’i2, Tamam El-Elimat2, Soraya Alnabulsi2 
1 Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Jordan
2 Department of Medicinal Chemistry, Faculty of Pharmacy, Jordan University of Science and Technology, Jordan

Correspondence Address:
Rana Obaidat
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology
Jordan

Background and purpose: Several pharmaceutical formulations were investigated to improve the solubility of 5-fluorouracil to enhance bioavailability and therapeutic efficacy. This study aimed to examine the potential use of cyclodextrin-based nanosponges for the incorporation of 5-fluorouracil and to investigate the use of different crosslinking agents on the properties of the resulting drug carrier. 5-Fluorouracil complexation with β-cyclodextrin was also studied to explain the unexpected results of weak 5-fluorouracil incorporation in nanosponge. Experimental approach: Nanosponges were synthesized by crosslinking β-cyclodextrin with two different crosslinkers; diphenyl carbonate and ethylenediaminetetraacetic dianhydride. The incorporation of 5-fluorouracil into β-cyclodextrin and the prepared nanosponges were assessed by NMR, FTIR, PXRD, DSC, and TGA. In addition, an in vitro release study was carried out to evaluate the potential use of β-cyclodextrin- based nanosponges as pharmaceutical formulations for 5-fluorouracil. Findings / Results: Physicochemical characterization of the dried formulations indicated the complexation of 5-fluorouracil with the β-cyclodextrin polymer. Despite that, no clear manifestation of 5-fluorouracil encapsulation in the prepared β-cyclodextrin-based nanosponge was detected. Furthermore, no significant differences were observed in the release profiles of 5-fluorouracil, β-cyclodextrin complex, and β- cyclodextrin-based nanosponge, suggesting weak complexation and instability in aqueous solutions. EDTA- crosslinked β-cyclodextrin-based nanosponge showed a slight improvement in 5-fluorouracil solubility with a faster initial rate of 5-fluorouracil release. Conclusion and implications: This study suggested weak complexation between 5-fluorouracil and the β- cyclodextrin polymer or nanosponges. Crosslinking of β-cyclodextrin with EDTA dianhydride crosslinker showed an enhancement in 5-fluorouracil saturation solubility combined with a faster initial rate of drug release.


How to cite this article:
Mashaqbeh H, Obaidat R, Al-Shar’i NA, El-Elimat T, Alnabulsi S. Weak complexation of 5-fluorouracil with β-cyclodextrin, carbonate, and dianhydride crosslinked β-cyclodextrin: in vitro and in silico studies.Res Pharma Sci 2022;17:334-349


How to cite this URL:
Mashaqbeh H, Obaidat R, Al-Shar’i NA, El-Elimat T, Alnabulsi S. Weak complexation of 5-fluorouracil with β-cyclodextrin, carbonate, and dianhydride crosslinked β-cyclodextrin: in vitro and in silico studies. Res Pharma Sci [serial online] 2022 [cited 2022 Aug 14 ];17:334-349
Available from: https://www.rpsjournal.net/article.asp?issn=1735-5362;year=2022;volume=17;issue=4;spage=334;epage=349;aulast=Mashaqbeh;type=0