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

• Published in: Polymer bulletin (Berlin, Germany) Germany), 2021-11, Vol.78 (11), p.6221-6250
• Main Authors: Yurtdaş-Kırımlıoğlu, Gülsel, Süzen-Demircioğlu, Yasemin, Berkman, Murat Sami, Metinoğlu-Örüm, Simge, Altun, Ebru
• Format: Article
• Language: English
• Subjects: Arthritis; Bioavailability; Biocompatibility; Biotransformation; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Complex Fluids and Microfluidics; Crosslinking; Drug delivery systems; Ibuprofen; Microspheres; Nonsteroidal anti-inflammatory drugs; Oral administration; Organic Chemistry; Original Paper; Particle size; Physical Chemistry; Polymer Sciences; Polymerization; Polymers; Polyphosphazenes; Self-assembly; Soft and Granular Matter; Synthesis; Thermodynamic properties; Trimers; Zeta potential
• ISSN: 0170-0839; 1436-2449
• DOI: 10.1007/s00289-020-03422-x

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.