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Facile synthesis of β-cyclodextrin-cyclophosphamide complex-loaded hydrogel for controlled release drug delivery

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Abstract

The research aims to develop cyclophosphamide-β-cyclodextrin complex-loaded hydrogels via free radical polymerization reaction by using hydroxypropyl methylcellulose (HPMC) as polymer, acrylic acid as monomer, ammonium per sulfate as initiator, and ethylene glycol dimethyl acrylate (EGDMA) as crosslinker. Nine formulations (HA1–HA9) were formulated to analyze the influence of process control parameters on cyclophosphamide release profile. Optimized preparation condition was investigated depending on substrate concentration, pH, and temperature. FTIR, DSC, TGA, and XRD were used to evaluate the compatibility of the excipients with cyclophosphamide, thermal stability of hydrogels, nature of pure cyclophosphamide, and drug-loaded hydrogel disks. Results showed that increasing concentration of polymer and monomer enhanced hydrogel swelling. However, increased crosslinker concentration resulted in decreased hydrogel swelling. In-vitro drug release studies showed maximum cyclophosphamide release occurred at pH 7.4. An acute oral toxicity assessment on rabbits revealed that the hydrogels were biocompatible with the biological system. This study proved that HPMC-co-AA (HA6 containing 0.6 gm HPMC, 0.9 gm acrylic acid, and 0.8 gm EGDMA)-based hydrogels can be an ideal candidate for achieving prolonged cyclophosphamide release.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan

    Nadiah Zafar, Muhammad Umar Ashraf & Sidra Mehr

  2. Department of Pharmacy, University of Chakwal, Chakwal, Pakistan

    Asif Mahmood

  3. Department of Pharmaceutics, College of Pharmacy, University of Sargodha, Sargodha, Pakistan

    Rai Muhammad Sarfraz

  4. Department of Pharmaceutics, Pak–Austria Fachhochschule: Institute of Applied Sciences and Technology, Haripur, Khyber Pakhtunkhwa, Pakistan

    Hira Ijaz

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  1. Nadiah Zafar
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Correspondence to Nadiah Zafar.

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Zafar, N., Mahmood, A., Sarfraz, R.M. et al. Facile synthesis of β-cyclodextrin-cyclophosphamide complex-loaded hydrogel for controlled release drug delivery. Polym. Bull. 80, 10939–10971 (2023). https://doi.org/10.1007/s00289-022-04567-7

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  • DOI: https://doi.org/10.1007/s00289-022-04567-7

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