PREPARATION AND CHARACTERIZATION OF NOVEL LOXOPROFEN-LOADED SOLID LIPID NANOPARTICLES
DOI:
https://doi.org/10.22159/ijap.2025v17i5.54465Keywords:
Solid lipid nanoparticles, Glyceryl monostearate, Loxoprofen, Probe ultrasonication, Controlled releaseAbstract
Objective: solid lipid nanoparticles (SLNs) exhibit many beneficial characteristics in the formulation of drug delivery systems. Loxoprofen (LX) is a non-steroidal anti-inflammatory drug (NSAID). This work aims to prepare and evaluate novel LX-loaded SLNs (LX-SLNs).
Methods: Experimental formulas were developed using Design-Expert 13. The Formulas were prepared via hot emulsification followed by probe ultrasonication then evaluated for their particle size, polydispersity index (PDI) and entrapment efficiency (EE%). The optimum formula was selected and lyophilized for further testing of fourier transformed-infrared spectroscopy (FTIR), powder x-ray diffraction (PXRD), and field emission scanning electronic microscopy (FE-SEM). In vitro release studies were conducted on pure LX and five formulas with varying lipid amounts and types.
Results: The optimization LX-SLNs formulations was performed using Design-Expert 13, with run 13 identified as the optimal formulation. This formulation, containing glyceryl monostearate (GMS) and poloxamer 407 (PX407), showed the best overall results in terms of particle size (70±4 nm), PDI (0.02±0.001), and EE% (88.07%±0.8). The release studies demonstrated sustained release behavior, with a decrease in the release rate as the lipid amount increased. Drug-excipient compatibility was confirmed by FTIR analysis, while PXRD results showed the disappearance of the sharp peaks found in the pure materials, indicating reduced crystallinity and suggesting that the drug is either in an amorphous form or dispersed in a solid solution state.
Conclusion: This study demonstrated successful encapsulation of LX in SLNs, with lipid content controlling the drug release rate. Higher lipid content demonstrated slower drug release.
References
1. Vargason AM, Anselmo AC, Mitragotri S. The evolution of commercial drug delivery technologies. Nat Biomed Eng. 2021;5(9):951-67. doi: 10.1038/s41551-021-00698-w, PMID 33795852.
2. Mekuye B, Abera B. Nanomaterials: an overview of synthesis classification, characterization and applications. Nano Select. 2023;4(8):486-501. doi: 10.1002/nano.202300038.
3. Areej W, Alhagiesa MM. Formulation and characterization of nimodipine nanoparticles for the enhancement of solubility and dissolution rate. Iraqi J Pharm Sci. 2021;30(2):10. doi 10.31351/vol30iss2pp143-152.
4. Scioli Montoto S, Muraca G, Ruiz ME. Solid lipid nanoparticles for drug delivery: pharmacological and biopharmaceutical aspects. Front Mol Biosci. 2020 Oct 30;7:587997. doi: 10.3389/fmolb.2020.587997, PMID 33195435.
5. Pham CV, Van MC, Thi HP, Thanh CD, Ngoc BT, Van BN. Development of ibuprofen-loaded solid lipid nanoparticle-based hydrogels for enhanced in vitro dermal permeation and in vivo topical anti-inflammatory activity. J Drug Deliv Sci Technol. 2020 Jun;57:101758. doi: 10.1016/j.jddst.2020.101758.
6. Ajaana SSA. Enhancing the loading capacity of kojic acid dipalmitate in liposomes. Lat Am J Pharm. 2020;39(7):1333-9.
7. Mohammad HA, MMG, Mohammd Akrami, Ameer Sabah Sahib. Design and characterization of tacrolimus monohydrate-loaded core-shell lipid polymer hybrid nanoparticle. J Complement Med Res. 2020;11(5):11.
8. Wannas AN, Abdul Hasan MT, Mohammed Jawad KK, Razzaq IF. Preparation and in vitro evaluation of SELF-NANO emulsifying drug delivery systems of ketoprofen. Int J Appl Pharm. 2023;15(3):71-9. doi: 10.22159/ijap.2023v15i3.46892.
9. Stanisic D, Costa AF, Cruz G, Duran N, Tasic L. Applications of flavonoids with an emphasis on hesperidin as anticancer prodrugs: phytotherapy as an alternative to chemotherapy. Studies in Natural Products Chemistry. 2018;58:161-212. doi: 10.1016/B978-0-444-64056-7.00006-4.
10. Mohammed HA, Khan RA, Singh V, Yusuf M, Akhtar N, Sulaiman GM. Solid lipid nanoparticles for targeted natural and synthetic drugs delivery in high incidence cancers and other diseases: roles of preparation methods lipid composition, transitional stability and release profiles in nanocarriers development. Nanotechnol Rev. 2023;12(1):20220517. doi: 10.1515/ntrev-2022-0517.
11. OPA, ND, Gidwani B. Optimization characterization and in vivo study of rivastigmine tartrate nanoparticles by using 22 full factorial design for oral delivery. Int J Appl Pharm. 2023;15(3):80-9. doi: 10.22159/ijap.2023v15i3.47140.
12. Dara T, Vatanara A, Nabi Meybodi M, Vakilinezhad MA, Malvajerd SS, Vakhshiteh F. Erythropoietin-loaded solid lipid nanoparticles: preparation optimization and in vivo evaluation. Colloids Surf B Biointerfaces. 2019 Jun 1;178:307-16. doi: 10.1016/j.colsurfb.2019.01.027, PMID 30878805.
13. Phalak SD, Bodke V, Yadav R, Pandav S, Ranaware M. A systematic review on nano drug delivery system: solid lipid nanoparticles (SLN). Int J Curr Pharm Res. 2024;16(1):10-20. doi: 10.22159/ijcpr.2024v16i1.4020.
14. S KS, G Rana D. Possible influence of loxoprofen in lipopolysaccharide-induced alterations in sucrose intake in chronic mild stress model in mice. Asian J Pharm Clin Res. 2021;14(7):99-101.
15. Peneva PT. Non-steroidal anti-inflammatory drugs for topical ophthalmic administration: contemporary trends. Int J Pharm Pharm Sci. 2015;7(9):13-9.
16. Hamza MY, Abd El Aziz ZR, Aly Kassem M, El Nabarawi MA. Loxoprofen nanosponges: formulation characterization and ex-vivo study. Int J Appl Pharm. 2022;14(2):233-41. doi: 10.22159/ijap.2022v14i2.43670.
17. Zaman M, Akhtar F, Baseer A, Hasan SM, Aman W, Khan A. Formulation development and in vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: a natural excipients-based approach. Pak J Pharm Sci. 2021;34(1):57-63. PMID 34248003.
18. Tak JW, Gupta B, Thapa RK, Woo KB, Kim SY, Go TG. Preparation and optimization of immediate release/sustained-release bilayered tablets of loxoprofen using box-behnken design. AAPS PharmSciTech. 2017;18(4):1125-34. doi: 10.1208/s12249-016-0580-5, PMID 27401334.
19. Nandgude T, PS P, VC P. Solid lipid nanoparticle-based gel to enhance topical delivery for acne treatment. Int J Drug Deliv Technol. 2022;13(2):474-82.
20. Arteaga Cabrera E, Ramirez Marquez C, Sanchez Ramirez E, Segovia Hernandez JG, Osorio Mora O, Gomez Salazar JA. Advancing optimization strategies in the food industry: from traditional approaches to multi-objective and technology-integrated solutions. Appl Sci. 2025;15(7). doi: 10.3390/app15073846.
21. Das S, Ng WK, Kanaujia P, Kim S, Tan RB. Formulation design preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: effects of process variables. Colloids Surf B Biointerfaces. 2011;88(1):483-9. doi: 10.1016/j.colsurfb.2011.07.036, PMID 21831615.
22. Rowe RC, Sheskey PJ, Owen SC. Handbook of pharmaceutical excipients. Vols. 308-10. London: Pharmaceutical Press; 2006. p. 501-2, 739.
23. Shrimal P, Jadeja G, Naik J, Patel S. Continuous microchannel precipitation to enhance the solubility of telmisartan with poloxamer 407 using box-behnken design approach. J Drug Deliv Sci Technol. 2019;53:101225. doi: 10.1016/j.jddst.2019.101225.
24. Shah M, Agrawal Y. High throughput screening: an in silico solubility parameter approach for lipids and solvents in SLN preparations. Pharm Dev Technol. 2013;18(3):582-90. doi: 10.3109/10837450.2011.635150, PMID 22107345.
25. Lee YC, Dalton C, Regler B, Harris D. Drug solubility in fatty acids as a formulation design approach for lipid-based formulations: a technical note. Drug Dev Ind Pharm. 2018;44(9):1551-6. doi: 10.1080/03639045.2018.1483395, PMID 29873584.
26. Cao Y, Marra M, Anderson BD. Predictive relationships for the effects of triglyceride ester concentration and water uptake on solubility and partitioning of small molecules into lipid vehicles. J Pharm Sci. 2004;93(11):2768-79. doi: 10.1002/jps.20126, PMID 15389678.
27. Alwani S, Wasan EK, Badea I. Solid lipid nanoparticles for pulmonary delivery of biopharmaceuticals: a review of opportunities challenges and delivery applications. Mol Pharm. 2024;21(7):3084-102. doi: 10.1021/acs.molpharmaceut.4c00128, PMID 38828798.
28. Yin J, Xiang C, Wang P, Yin Y, Hou Y. Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability. Int J Nanomedicine. 2017 Apr 10;12:2923-31. doi: 10.2147/IJN.S131167, PMID 28435268, PMCID PMC5391827.
29. Farrell E, Brousseau JL. Guide for DLS sample preparation; 2025. p. 1-3.
30. Chemical instrumentation F. Particle characterization guide; 1990.
31. Alhagiesa A, Ghareeb M. Formulation and evaluation of nimodipine nanoparticles incorporated within orodispersible tablets. International Journal of Drug Delivery Technology. 2020;10(4):547-52. doi: 10.25258/ijddt.10.4.7.
32. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2):57. doi: 10.3390/pharmaceutics10020057, PMID 29783687.
33. Mehta M, Bui TA, Yang X, Aksoy Y, Goldys EM, Deng W. Lipid-based nanoparticles for drug/gene delivery: an overview of the production techniques and difficulties encountered in their industrial development. ACS Mater Au. 2023;3(6):600-19. doi: 10.1021/acsmaterialsau.3c00032, PMID 38089666.
34. Xie S, Zhu L, Dong Z, Wang X, Wang Y, Li X. Preparation characterization and pharmacokinetics of enrofloxacin-loaded solid lipid nanoparticles: influences of fatty acids. Colloids Surf B Biointerfaces. 2011;83(2):382-7. doi: 10.1016/j.colsurfb.2010.12.014, PMID 21215599.
35. Khezri K, Saeedi M, Morteza Semnani K, Akbari J, Hedayatizadeh Omran A. A promising and effective platform for delivering hydrophilic depigmenting agents in the treatment of cutaneous hyperpigmentation: kojic acid nanostructured lipid carrier. Artif Cells Nanomed Biotechnol. 2021;49(1):38-47. doi: 10.1080/21691401.2020.1865993, PMID 33438443.
36. Khairnar SV, Pagare P, Thakre A, Nambiar AR, Junnuthula V, Abraham MC. Review on the scale-up methods for the preparation of solid lipid nanoparticles. Pharmaceutics. 2022;14(9):1886. doi: 10.3390/pharmaceutics14091886, PMID 36145632.
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