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Peer-reviewedCC BY 4.0Pharmaceutical Research

Development of Sustained Release Chitosan/β-Glycerol Phosphate-Based Injectable Thermo-Gels Containing Naproxen Sodium: In-Vitro and In-Vivo Evaluation

7 affiliations
  1. 1Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan
  2. 2Department of Pharmaceutics, Bahauddin Zakariya University, Multan, Pakistan
  3. 3The Next Institute of Science and Technology, Multan, Pakistan
  4. 4Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
  5. 5Leicester School of Pharmacy, De Montfort University, Leicester, UK
  6. 6College of Engineering, Design and Physical Sciences, Brunel University of London, London, UK
  7. 7Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK

Abstract

Purpose: To develop in-situ chitosan/β-glycerol phosphate (β-GP) thermogels loaded with naproxen sodium for sustained drug delivery, to circumvent issues related with prolonged oral administration of naproxen (e.g. ulceration, abdominal discomfort, diarrhoea, bloating, etc.). To overcome these complications, in-situ gel formulations are developed as a promising strategy for long-term management of chronic inflammatory disorders such as arthritis. Furthermore, this system is evaluated with an earlier naproxen formulation prepared using sodium alginate.

Methods: Thermogels containing varying chitosan concentrations were prepared at pH 7.4 and 37°C, followed by drug loading. Key physicochemical properties, including injectability, gelation time, and sol–gel fraction, were evaluated. In-vitro release studies were conducted using a dialysis membrane with a USP dissolution basket apparatus-I. Anti-inflammatory efficacy was assessed in Sprague–Dawley rats with carrageenan-induced hind ankle inflammation.

Results: Results indicated that formulations with higher polymer content exhibited shorter gelation times and increased gel fractions. In-vitro release from F6CGP demonstrated sustained naproxen sodium delivery, following the Korsmeyer-Peppas model with Fickian diffusion kinetics (n ≤ 0.45). In-vivo, the swelling of the inflamed hind ankle joint decreased progressively over 72 h (≈ -2.6 ± 0.73 mm), confirming effective anti-inflammatory action; relatively better as compared to the previous sodium alginate system.

Conclusions: In-situ chitosan/β-glycerol gel-forming injectable formulation F6CGP provides sustained naproxen sodium release and shows potential as a therapeutic strategy for chronic inflammatory conditions such as arthritis. The results also indicate that this polymeric system can play a key role in modulating critical formulation parameters i.e. gelation time, gel fraction, injectability, drug release etc.

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BibTeX
@article{ahmad2026development,
  title = {{Development of Sustained Release Chitosan/β-Glycerol Phosphate-Based Injectable Thermo-Gels Containing Naproxen Sodium: In-Vitro and In-Vivo Evaluation}},
  author = {Hassan Ahmad and Sadia Jafar Rana and Tahir Ali Chohan and Haashim Iqbal and Rawdha Benziane and Manoochehr Rasekh and Saman Zafar and Muhammad Sohail Arshad and Zeeshan Ahmad},
  journal = {Pharmaceutical Research},
  year = {2026},
  month = sep,
  doi = {10.1007/s11095-026-04197-y},
  url = {https://doi.org/10.1007/s11095-026-04197-y},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Development of Sustained Release Chitosan/β-Glycerol Phosphate-Based Injectable Thermo-Gels Containing Naproxen Sodium: In-Vitro and In-Vivo Evaluation
AU  - Hassan Ahmad
AU  - Sadia Jafar Rana
AU  - Tahir Ali Chohan
AU  - Haashim Iqbal
AU  - Rawdha Benziane
AU  - Manoochehr Rasekh
AU  - Saman Zafar
AU  - Muhammad Sohail Arshad
AU  - Zeeshan Ahmad
PY  - 2026
DA  - 2026/09/22
JO  - Pharmaceutical Research
DO  - 10.1007/s11095-026-04197-y
UR  - https://doi.org/10.1007/s11095-026-04197-y
AB  - Purpose: To develop in-situ chitosan/β-glycerol phosphate (β-GP) thermogels loaded with naproxen sodium for sustained drug delivery, to circumvent issues related with prolonged oral administration of naproxen (e.g. ulceration, abdominal discomfort, diarrhoea, bloating, etc.). To overcome these complications, in-situ gel formulations are developed as a promising strategy for long-term management of chronic inflammatory disorders such as arthritis. Furthermore, this system is evaluated with an earlier naproxen formulation prepared using sodium alginate.  Methods: Thermogels containing varying chitosan concentrations were prepared at pH 7.4 and 37°C, followed by drug loading. Key physicochemical properties, including injectability, gelation time, and sol–gel fraction, were evaluated. In-vitro release studies were conducted using a dialysis membrane with a USP dissolution basket apparatus-I. Anti-inflammatory efficacy was assessed in Sprague–Dawley rats with carrageenan-induced hind ankle inflammation.  Results: Results indicated that formulations with higher polymer content exhibited shorter gelation times and increased gel fractions. In-vitro release from F6CGP demonstrated sustained naproxen sodium delivery, following the Korsmeyer-Peppas model with Fickian diffusion kinetics (n ≤ 0.45). In-vivo, the swelling of the inflamed hind ankle joint decreased progressively over 72 h (≈ -2.6 ± 0.73 mm), confirming effective anti-inflammatory action; relatively better as compared to the previous sodium alginate system.  Conclusions: In-situ chitosan/β-glycerol gel-forming injectable formulation F6CGP provides sustained naproxen sodium release and shows potential as a therapeutic strategy for chronic inflammatory conditions such as arthritis. The results also indicate that this polymeric system can play a key role in modulating critical formulation parameters i.e. gelation time, gel fraction, injectability, drug release etc.
SN  - 0724-8741
SN  - 1573-904X
ER  -