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Synthesis, spectroscopic, thermal properties, in vitro release, and stability studies of ibuprofen-loaded microspheres cross-linked with hexachlorocyclotriphosphazene/octachlorocyclotetraphosphazene

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Abstract

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties used to treat rheumatoid arthritis, osteoarthritis, and mild to moderate pain. However, it has extremely low aqueous solubility, rapid biotransformation with a half-life of nearly 2 h and poor tissue absorption resulting in poor bioavailability. One of the most important strategies for avoiding NSAID-related toxicity is modified release polymeric systems. Cross-linked polyphosphazene microspheres are attractive systems in drug delivery, as they are biocompatible and biodegradable. In the current work, novel cross-linked inorganic hybrid polyphosphazene microspheres were synthesized by self-assembly precipitation polymerization between hexachlorocyclotriphosphazene (trimer)/octachlorocyclotetraphosphazene (tetramer) as a cross-linker and 4,7-dihydroxyisoflavone (4.7 DHF) as a monomer. The structure of synthesized microspheres was identified several techniques in detail. IBU was successfully incorporated into the trimeric and tetrameric polyphosphazene microspheres. Particle size, zeta potential, drug loading, morphology, thermal, FT-IR, and XRD analyses, and IBU quantification using UPLC method were carried out to evaluate the microspheres. Considering the higher drug loading values and smaller particle size, trimer-based microspheres (4.7 DHF-TRI-IBU) were selected for further studies. In vitro release studies from 4.7 DHF-TRI-IBU demonstrated modified release pattern which followed zero-order kinetic model. Characteristics of 4.7 DHF-TRI-IBU were found to remain stable at 4 °C ± 1 °C, 25 °C  ± 1 °C and 40 °C ± 1 °C during the storage period of 3 months. In vitro characterization analyses showed that spherical, micron-sized 4.7 DHF-TRI-IBU microspheres with prolonged release pattern has the potential of enhancing analgesic and anti-inflammatory activity.

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Acknowledgement

The authors would like to thank to Abdi İbrahim (İstanbul, Turkey) for supplying a gift sample of ibuprofen, Management of BİBAM (Anadolu University) and Eskişehir Technical University for providing an opportunity in performing SEM, XRD and BET analyses. This study was financed by Anadolu University Scientific Research Project Foundation (No: 1706S377).

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey

    Gülsel Yurtdaş-Kırımlıoğlu & Murat Sami Berkman

  2. Depatment of Inorganic Chemistry, Faculty of Science, Eskişehir Technical University, Eskişehir, Turkey

    Yasemin Süzen-Demircioğlu & Ebru Altun

  3. Depatment of Inorganic Chemistry, Faculty of Science, Burdur Mehmet Akif Ersoy University, Burdur, Turkey

    Simge Metinoğlu-Örüm

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  1. Gülsel Yurtdaş-Kırımlıoğlu
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Yurtdaş-Kırımlıoğlu, G., Süzen-Demircioğlu, Y., Berkman, M.S. et al. Synthesis, spectroscopic, thermal properties, in vitro release, and stability studies of ibuprofen-loaded microspheres cross-linked with hexachlorocyclotriphosphazene/octachlorocyclotetraphosphazene. Polym. Bull. 78, 6221–6250 (2021). https://doi.org/10.1007/s00289-020-03422-x

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