Formulation and Characterization of Nefopam Hydrochloride-Loaded Niosomes for Enhanced Analgesic Drug Delivery
Abstract
Background: Nefopam Hydrochloride (NF-HCl) is a centrally acting non-opioid analgesic with limited oral bioavailability due to first-pass metabolism. To overcome this limitation and provide sustained drug release, niosomal drug delivery systems were explored.
Objective: To formulate and characterize NF-HCl-loaded niosomes using Span surfactants and cholesterol via Hand Shaking Method (HSM) and Ether Injection Method (EIM), and evaluate their physicochemical and drug release properties.
Methods: Twelve niosomal formulations were prepared using three non-ionic surfactants (Span 20, 40, and 60) in 1:1 and 2:1 molar ratios with cholesterol. The formulations were evaluated for entrapment efficiency (EE%), vesicle size, morphology, zeta potential, in vitro drug release, and drug release kinetics.
Results: Among the formulations, PNF-9 (Span 60:CH, 1:1, EIM) showed the highest EE (58.94%), sustained drug release (58.82% over 8 hours), and a zeta potential of −64.6 mV. Drug release kinetics followed the Korsmeyer-Peppas model with an R² value of 0.9965, indicating non-Fickian diffusion. Stability studies confirmed greater retention at 4–8°C.
Conclusion: The optimized NF-HCl niosomal formulation (PNF-9) prepared via EIM using Span 60 exhibited promising characteristics for sustained and targeted analgesic delivery, potentially enhancing therapeutic efficacy and patient compliance.
Keywords: Niosomes, Nefopam Hydrochloride, Span 60, Entrapment Efficiency, Drug Release Kinetics, Ether Injection Method
Keywords:
Niosomes, Nefopam Hydrochloride, Span 60, Entrapment Efficiency, Drug Release Kinetics, Ether Injection MethodDOI
https://doi.org/10.22270/jddt.v15i7.7279References
1. Ahmed HM, Jaafar IS. Nefopam HCl in situ mucoadhesive liquid suppository, a potential drug delivery system to enhance bioavailability. F1000Research. 2025 Feb 4;14:160. https://doi.org/10.12688/f1000research.159557.1
2. El Hashemy HA, Salama A, Rashad A. Novel In Situ Gel for Molnupiravir-Loaded Niosomes: Design, In Vitro Characterization and In Vivo Evaluation. Egyptian Journal of Chemistry. 2024 Oct 1;67(10):257-68.
3. Gao S, Sui Z, Jiang Q, Jiang Y. Functional Evaluation of Niosomes Utilizing Surfactants in Nanomedicine Applications. International Journal of Nanomedicine. 2024 Dec 31:10283-305. https://doi.org/10.2147/IJN.S480639 PMid:39403709 PMCid:PMC11472738
4. Taha E, Shetta A, Nour SA, Naguib MJ, Mamdouh W. Versatile Nanoparticulate Systems as a Prosperous Platform for Targeted Nose-Brain Drug Delivery. Molecular Pharmaceutics. 2024 Feb 8;21(3):999-1014. https://doi.org/10.1021/acs.molpharmaceut.3c00588 PMid:38329097
5. Prashar P, Sood A, Gautam A, Sharma PK, Kumar B, Melkani I, Panchal S, Singh SK, Gulati M, Pandey NK, Dash L. Nanotechnology-Mediated Strategy for the Treatment of Neuropathic Pain: A Promising Approach. InNanotechnology 2020 Oct 18 (pp. 131-168). CRC Press. https://doi.org/10.1201/9781003082859-10
6. Alabdly A, Kassab HJ. Formulation variables effect on gelation temperature of nefopam hydrochloride intranasal in situ gel (Conference Paper). Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2022;31(Suppl.):32-44. https://doi.org/10.31351/vol31issSuppl.pp32-44
7. Gupta P, Yadav KS. Formulation and evaluation of brinzolamide encapsulated niosomal in-situ gel for sustained reduction of IOP in rabbits. Journal of Drug Delivery Science and Technology. 2022 Jan 1;67:103004. https://doi.org/10.1016/j.jddst.2021.103004
8. Teron C, Bhuyan A, Saikia P, Dutta SR, Gogoi H, Rongpi S. A Comprehensive Review on Niosomes in Drug Delivery and Recent Advancements. Journal of Drug Delivery & Therapeutics. 2024 Sep 1;14(9). https://doi.org/10.22270/jddt.v14i6.6651
9. Teaima MH, Helal DA, Alsofany JM, El-Nabarawi MA, Yasser M. Ion-triggered in situ gelling intranasal spray of dronedarone hydrochloride nanocarriers: in vitro optimization and in vivo pharmacokinetic appraisal. Pharmaceutics. 2022 Nov 8;14(11):2405. https://doi.org/10.3390/pharmaceutics14112405 PMid:36365223 PMCid:PMC9694345
10. K Shukla S, Nguyen V, Goyal M, Gupta V. Cationically modified inhalable nintedanib niosomes: enhancing therapeutic activity against non-small-cell lung cancer. Nanomedicine. 2022 Jun 1;17(13):935-58. https://doi.org/10.2217/nnm-2022-0045 PMid:36004583 PMCid:PMC9583758
11. Birla D, Khandale N, Bashir B, ShahbazAlam M, Vishwas S, Gupta G, Dureja H, Kumbhar PS, Disouza J, Patravale V, Veiga F. Application of quality by design in optimization of nanoformulations: Principle, perspectives and practices. Drug Delivery and Translational Research. 2025 Mar;15(3):798-830. https://doi.org/10.1007/s13346-024-01681-z PMid:39126576
12. Albassam NY, Kassab HJ. Diacerein loaded novasome for transdermal delivery: Prepartion, in-vitro characterization and factors affecting formulation. Iraqi Journal of Pharmaceutical Sciences. 2023 Nov 3;32(Suppl.):214-24. https://doi.org/10.31351/vol32issSuppl.pp214-224
13. Ali SK, Al-Akkam EJ. Effects of different types of bile salts on the physical properties of ropinirole-loaded bilosomes. Al-Rafidain Journal of Medical Sciences (ISSN 2789-3219). 2023 Aug 11;5:134-42. https://doi.org/10.54133/ajms.v5i.176
14. Kisku A, Nishad A, Agrawal S, Paliwal R, Datusalia AK, Gupta G, Singh SK, Dua K, Sulakhiya K. Recent developments in intranasal drug delivery of nanomedicines for the treatment of neuropsychiatric disorders. Frontiers in Medicine. 2024 Sep 19;11:1463976. https://doi.org/10.3389/fmed.2024.1463976 PMid:39364023 PMCid:PMC11446881
15. Chettupalli AK, Ajmera S, Kuchukuntla M, Palanivel V, Katta S. Design Formulation of Nanospanlastic Novel Carriers as a Promising Approach to Enhanced Bioavailability in Intranasal Drug Delivery for Sinusitis: Statistical Optimization and In vitro and In vivo Characterization. Current Nanomedicine (Formerly: Recent Patents on Nanomedicine). 2024 Nov 1;14(3):266-88. https://doi.org/10.2174/0124681873262019231105201433
16. Abdallah MH, El-Horany HE, El-Nahas HM, Ibrahim TM. Tailoring risperidone-loaded glycethosomal in situ gels using Box-Behnken design for treatment of schizophrenia-induced rats via intranasal route. Pharmaceutics. 2023 Oct 24;15(11):2521. https://doi.org/10.3390/pharmaceutics15112521 PMid:38004501 PMCid:PMC10675145
17. Singh A, Arora S, Singh TG. Development and optimization of Andrographis paniculata extract-loaded phytosomes using Box-Behnken design approach. Journal of Integrated Science and Technology. 2023 Jan 24;11(4):558-.
18. Salem HF, Kharshoum RM, Awad SM, Ahmed Mostafa M, Abou-Taleb HA. Tailoring of retinyl palmitate-based ethosomal hydrogel as a novel nanoplatform for acne vulgaris management: Fabrication, optimization, and clinical evaluation employing a split-face comparative study. International Journal of Nanomedicine. 2021 Jun 24:4251-76. https://doi.org/10.2147/IJN.S301597 PMid:34211271 PMCid:PMC8239256
19. Reddy SJ, Mutalik S, Viswanatha GL, Kumar G, John J, Chamallamudi MR, Das A, Das S, Nandakumar K. Nose-to-brain Drug Delivery System: An Emerging Approach to Chemotherapy-induced Cognitive Impairment. Pharmaceutical Nanotechnology. 2025 Feb;13(1):212-238. https://doi.org/10.2174/0122117385291482240426101519 PMid:38757164
20. Prashar P, Sood A, Gautam A, Sharma PK, Kumar B, Melkani I, Panchal S, Singh SK, Gulati M, Pandey NK, Dash L. Nanotechnology-Mediated Strategy for the Treatment of Neuropathic Pain: A Promising Approach. InNanotechnology 2020 Oct 18 (pp. 131-168). CRC Press. https://doi.org/10.1201/9781003082859-10
21. Wen P, Ren C. Research progress on intranasal treatment for Parkinson's disease. Neuroprotection. 2024 Jun;2(2):79-99. https://doi.org/10.1002/nep3.42
22. ALWAN OM, JAFAR IS. Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system. Journal of Research in Pharmacy. 2024 Sep 1;28(5). https://doi.org/10.29228/jrp.825
23. Alwan OM, Jafar IS. Formulation and Characterization of Poloxamer-Based Mucoadhesive Vaginal In Situ Gelling System of Miconazole Nitrate. Hilla University College Journal For Medical Science. 2024;2(3):32-39. https://doi.org/10.62445/2958-4515.1029
Published
Abstract Display: 413 
PDF Downloads: 317 PDF Downloads: 48 How to Cite
Issue
Section
Copyright (c) 2025 Garvendra Singh Rathore, Ravi Prakash Soni, Vinesh Kumar
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.