An Insightful Study on SMEDDS Challenges and Potential Strategies

Year : 2025 | Volume : 13 | Special Issue 02 | Page : 311 334
    By

    Bhavani B,

  • B.V.S.S.Subhadra,

  • J.Divya Bhavani,

  • M.Surya Kiran,

  • M.Jyothsna,

  • P. Nookaratnam,

  • G.Venkataramana,

  1. Professor & Head of the Pharmacy, Department of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India
  2. Student, Department of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India
  3. Student, Department of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India
  4. Student, Department of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India
  5. Student, Department of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India
  6. Student, Department of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India
  7. Student, Department of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India

Abstract

Self-microemulsifying drug delivery systems (SMEDDS) have gained attention as an effective approach to enhance the bioavailability of poorly water-soluble drugs. They are innovative lipid-based formulations designed to enhance the solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs. The development of SMEDDS involves systematic selection of components based on solubility and emulsification efficiency, followed by optimization of ratios using pseudo-ternary phase diagrams. The resulting formulations are evaluated for droplet size, zeta potential, self-emulsification efficiency, and thermodynamic stability to ensure efficacy and reproducibility. SMEDDS can be conveniently encapsulated in soft or hard gelatin capsules, providing a patient-friendly oral delivery platform. Nevertheless, they are not without drawbacks, such as drug precipitation in vivo, challenges in formulation handling, restricted lymphatic absorption, absence of reliable in vitro prediction methods, and the oxidative degradation of unsaturated fatty acids. These issues limit the broader application. Incorporating polymers or precipitation inhibitors into lipid-based systems can help sustain drug supersaturation after dispersion, improving bioavailability and minimizing variability in drug exposure. Furthermore, converting liquid SMEDDS to solid form can alleviate problems related to handling and stability. The inclusion of medium-chain triglycerides (MCT) and antioxidants also helps counteract the oxidation of unsaturated fatty acids, addressing key limitations. SMEDDS represent a promising approach for overcoming the solubility and bioavailability challenges of lipophilic drugs, with potential applications in both pharmaceutical research and commercial drug development. Future advancements in component selection, nanotechnology integration, and personalized medicine are expected to further expand their utility in addressing unmet clinical needs. This review offers an in-depth exploration of SMEDDS challenges and proposes strategies to overcome them.

Keywords: Self-microemulsifying drug delivery systems, limitations, techniques, invivo studies, analytical techniques.

[This article belongs to Special Issue under section in Journal of Polymer and Composites (jopc)]

How to cite this article:
Bhavani B, B.V.S.S.Subhadra, J.Divya Bhavani, M.Surya Kiran, M.Jyothsna, P. Nookaratnam, G.Venkataramana. An Insightful Study on SMEDDS Challenges and Potential Strategies. Journal of Polymer and Composites. 2025; 13(02):311-334.
How to cite this URL:
Bhavani B, B.V.S.S.Subhadra, J.Divya Bhavani, M.Surya Kiran, M.Jyothsna, P. Nookaratnam, G.Venkataramana. An Insightful Study on SMEDDS Challenges and Potential Strategies. Journal of Polymer and Composites. 2025; 13(02):311-334. Available from: https://journals.stmjournals.com/jopc/article=2025/view=205077


Browse Figures

References

  1. Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov Today. 2008; 13:606–12.
  2. Yao G, Li Y. Preparation, characterization and evaluation of self-microemulsifying drug delivery systems (SMEDDS) of Ligusticum chuanxiong oil. Biomed Prev Nutr. 2010;1(1):36–42.
  3. You J, Cui FD, Li QP. A novel formulation design about water-insoluble oily drug: preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits. Int J Pharm. 2005; 288:315–23.
  4. Hauss DJ. Oral lipid-based formulations. Adv Drug Deliv Rev. 2007; 59:667–76.
  5. Eccleston GM. Emulsions and microemulsions. In: Swarbrick J, editor. Encyclopedia of pharmaceutical technology. Vol. 3. New York: Informa Healthcare; 2007. p. 1548–65.
  6. Anton N, Vandamme TF. Nano-emulsions and micro-emulsions: Clarifications of the critical differences. Pharm Res. 2010;28:978–85
  7. Rahman A, Hussain A, Hussain S, et al. Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery systems (SEDDS/SMEDDS). Drug Dev Ind Pharm. 2012; 39:1–19.
  8. Lawrence MJ, Warisnoicharoen W. Recent advances in microemulsions as drug delivery vehicles. In: Torchilin VP, ed. Nanoparticulates as drug carriers. London: Imperial College Press; 2006:125–60.
  9. Boyd BJ, Nguyen TH, Mullertz A. Lipids in oral controlled-release drug delivery. In: Wilson CG, Crowley PJ, eds. Controlled Release in Oral Drug Delivery. New York: Springer; 2011. p. 299–321.
  10. Wei Y, Ye X, Shang X, et al. Enhanced oral bioavailability of silybin by a supersaturatable self-emulsifying drug delivery system (S-SEDDS). Colloids Surf A Physicochem Eng Aspects. 2012; 396:22–8.
  11. Xi J, Chang CK, Meng ZY, et al. Formulation development and bioavailability evaluation of a self-nanoemulsified drug delivery system of oleanolic acid. AAPS PharmSciTech. 2009; 10:172–82.
  12. Shahba AAW, Mohsin K, Alanazi FK. The studies of phase equilibria and efficiency assessment for self-emulsifying lipid-based formulation. AAPS PharmSciTech. 2012; 13:522–33.
  13. Wang Z, Sun J, Wang Y, et al. Solid self-emulsifying nitrendipine pellets: preparation and in vitro/in vivo evaluation. Int J Pharm. 2010; 38:1–6.
  14. Pouton CW. Lipid formulations for oral administration of drugs: Non-emulsifying, self-emulsifying, and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci. 2000;11(2): S93–S98.
  15. Wadhwa J, Nair A, Kumria R. Emulsion forming drug delivery system for lipophilic drugs. Acta Pol Pharm Drug Res. 2012; 69:179–91.
  16. Zidan AS, Sammour OA, Hammad MA, et al. Quality by design: understanding the product variability of a self-nanoemulsified drug delivery system of cyclosporine A. J Pharm Sci. 2007;96:2409–23
  17. Gao P, Shi Y. Characterization of supersaturable formulations for improved absorption of poorly soluble drugs. AAPS Pharm Sci Tech. 2012; 14:703–13.
  18. Land LM, Li P, Bummer PM. The influence of water content of triglyceride oils on the solubility of steroids. Pharm Res. 2005; 22:784–8.
  19. Azaz E, Donbrow M, Hamburger R. Incompatibility of non-ionic surfactants with oxidizable drugs. Pharm J. 1973; 211:15.
  20. Parmar N, Singla N, Amina S, Kohli K. Study of co-surfactant effect on nanoemulsifying area and development of lercanidipine-loaded self-nanoemulsifying drug delivery system (SNEDDS). Colloids Surf B. 2011; 86:327–38.
  21. Dai WG. In vitro methods to assess drug precipitation. Int J Pharm. 2010; 393:1–16.
  22. Mullin JW. Nucleation. In: Crystallization. 4th ed. London: Butterworth-Heinemann; 2001:181–215.
  23. Bevernage J, Brouwers J, Brewster ME, Augustijns P. Evaluation of gastrointestinal drug supersaturation and precipitation: Strategies and issues. Int J Pharm. 2013; 453:25–35.
  24. Warren DB, Benameur H, Porter CJH, Pouton CV. Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: a mechanistic basis for utility. J Drug Target. 2010; 18:704–31.
  25. Avdeef A. Absorption and drug development solubility, permeability, and charge state. New Jersey: Wiley-Interscience; 2003. p. 91–5.
  26. Kashchiev D, Van Rosmalen GM. Nucleation in solutions revisited. Cryst Res Technol. 2003; 38:555–74.
  27. Plaizier-Vercammen JA, De Nève RE. Interaction of povidone with aromatic compounds II: evaluation of ionic strength, buffer concentration, temperature, and pH by factorial analysis. J Pharm Sci. 1981; 70:1252–6.
  28. Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007; 6:231–8.
  29. Gao P, Morozowich W. Development of supersaturable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs. Expert Opin Drug Deliv. 2006; 3:97–110.
  30. Chen ZQ, Liu Y, Zhao JH, et al. Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system. Int J Nanomed. 2012; 7:1115–25.
  31. Mathews C, Sugano K. Supersaturable formulations. Drug Deliv Sys. 2010;25–4:371–4.
  32. Sirois P. Feasibility assessment and considerations for scaling initial prototype lipid-based formulations to phase I/II clinical trial batches. In: Hauss DJ, ed. Oral Lipid-Based Formulations Enhancing the Bioavailability of Poorly Water-Soluble Drugs, vol. 170. New York: Informa Healthcare; 2007:63–77.
  33. Bessho M, Kojima T, Okuda S, Hara M. Radiation-induced cross-linking of gelatin by using γ-rays: Insoluble gelatin hydrogel formation. Bull Chem Soc Japan. 2007; 80:979–85.
  34. Albert K, Bayer E, Worsching A, Vogele H. Investigation of the hardening reaction of gelatin with 13C labeled formaldehyde by solution and solid-state 13C NMR spectroscopy. Z Naturforsch. 1991; 46:385–9.
  35. Gullapalli PR. Soft gelatin capsules (Softgels). J Pharm Sci. 2010; 99:4107–48.
  36. Adesunloye A, Stach P. Reduction of gelatin cross-linking. Pharmaceutical Development and Technology. 1998; 24:494–500.
  37. Serajuddin ATM, Sheen PC, Augustine MA. Water migration from soft gelatin capsule shell to fill material and its effect on drug solubility. J Pharm Sci. 1986; 75:62–4.
  38. Brox W. Gelatin capsule. US Patent. 1988a;4,780,316.
  39. Brox W. Soft gelatin capsules and methods for their production. US Patent. 1988b;4,744,988.
  40. Moreton RC, Armstrong NA. Design and use of an apparatus for measuring diffusion through glycerogelatin films. Int J Pharm. 1995; 122:79–89.
  41. Gao P, Morozowich W. Improving the oral absorption of poorly soluble drugs using SEDDS and S-SEDDS formulations. In: Qiu Y, Chen Y, Zhang GGZ, editors. Developing solid oral dosage forms: theory and practice. New York: Academic Press; 2009. p. 443–9.
  42. Ku MS, Li W, Dulin W, et al. Performance qualification of a new hypromellose capsule: Part I. Comparative evaluation of physical, mechanical and processability quality attributes of Vcaps Plus®, QualiV® and gelatin capsules. Int J Pharm. 2010; 386:30–41.
  43. Nekkanti VK, Karatg PK, Prabhu R, Pillai R. Solid self-microemulsifying formulation of candesartan cilexetil. AAPS PharmSciTech. 2010; 2:9–17.
  44. Mu H, Holm R, Müllertz A. Lipid-based formulations of oral administration of poorly water-soluble drugs. Int J Pharm. 2013; 453:215–24.
  45. Christensen KL, Pedersen GP, Kristensen HG. Preparation of redispersible dry emulsions by spray drying. Int J Pharm. 2001; 212:187–94.
  46. Janga KY, Jukanti R, Sunkavalli S, et al. In-situ absorption and relative bioavailability studies of Zaleplon loaded self-nanoemulsifying powders. J Microencapsul. 2012; 30:161–72.
  47. Nazzal S, Khan MA. Controlled release of a self-emulsifying formulation from a tablet dosage form: stability assessment and optimization of some processing parameters. Int J Pharm. 2006; 315:110–21.
  48. Hu X, Lin C, Chen D, et al. Sirolimus solid self-microemulsifying pellets: formulation development, characterization and bioavailability evaluation. Int J Pharm. 2012; 438:123–33.
  49. Yi X, Wan J, Xu H, Yang X. A new solid self-microemulsifying formulation prepared by spray-drying to improve the oral bioavailability of poorly water-soluble drugs. Eur J Pharm Biopharm. 2008; 70:439–44.
  50. Hentzschel CM, Alnaief M, Smirnova I, et al. Tabletting properties of silica aerogel and other silicates. Drug Dev Ind Pharm. 2012; 38:462–7.
  51. Patel AR, Vavia PR. Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate. AAPS J. 2007;9(3): E344–E352.
  52. Bali V, Ali M, Ali J. Nanocarrier for the enhanced bioavailability of a cardiovascular agent: In vitro, pharmacodynamic, pharmacokinetic, and stability assessment. International Journal of Pharmaceutics. 2011;403(1–2):45–56.
  53. Avasarala H, Dinakaran SK, Kakaraparthy R, Jayanti VR. Self-emulsifying drug delivery system for enhanced solubility of asenapine maleate: Design, characterization, in vitro, ex vivo and in vivo appraisal. Drug Development and Industrial Pharmacy. 2019;45(4):548–59.
  54. Balakrishnan P, Lee B-J, Oh DH, et al. Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems. International Journal of Pharmaceutics. 2009;374(1–2):66–72.
  55. Elnaggar YSR, El-Massik MA, Abdallah OY. Self-nanoemulsifying drug delivery systems of tamoxifen citrate: design and optimization. Int J Pharm. 2009;380(1–2):133–41. doi:10.1016/j.ijpharm.2009.07.015.
  56. Karamustafa F, Ćelebi N. Development of an oral microemulsion formulation of alendronate: Effects of oil & co-surfactant type on phase behaviour. J Microencapsulation. 2008;25(5):315–323.
  57. Avasarala Harani, Nokku Rasi, Pabbineedi Ratnam et al., Design and statistical optimization of concentration of sublimating agents in formulating orodispersive tablets, Indian Drugs, 2023, 60(9), 108 – 111.
  58. Avasarala Harani, Kumar D Sathis, Tripathy Srijit et al., Design and Statistical Optimization of Pluronic Based Ibuprofen Gels by Box-Behnken Design and Their Physicochemical Characterization, Pharmaceutical Chemistry Journal, 2023, 57(1), 129 – 137.
  59. Avasarala Harani, Dinakaran Sathiskumar, Boddeda Bhavani et al., Ethosomal gel: a novel choice for topical delivery of the antipsychotic drug Ziprasidone Hydrochloride, Brazilian Journal of Pharmaceutical Sciences, 2022, 58, e19317.
  60. Gowripattapu S, Kumar DS, Selvamuthukumar S. Formulation and Statistical Evaluation of Tablets Containing Pitavastatin-Self Nano Emulsifying Drug Delivery Systems, Current Drug Delivery, 2023, 20(4), 414–432.
  61. Gradzielski M. Recent developments in the characterisation of microemulsions. Curr Opin Colloid Interface Sci. 2008;13(4):263–269.
  62. Singh AK, Chaurasiya A, Awasthi A, et al. Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS). AAPS PharmSciTech. 2009;10(3):906–16.
  63. Hauss DJ, Mehta SC, Radebaugh GW. Targeted lymphatic transport and modified systemic distribution of CI-976, a lipophilic lipid regulator drug, via a formulation approach. Int J Pharm. 1994; 108:85–93.
  64. Boyd M, Risovic V, Jull P, et al. A stepwise surgical procedure to investigate the lymphatic transport of lipid-based oral drug formulations: Cannulation of the mesenteric and thoracic lymph ducts within the rat. J Pharmacol Toxicol Method. 2004; 49:115–20.
  65. Dahan A, Hoffman A. Evaluation of a chylomicron flow blocking approach to investigate the intestinal lymphatic transport of lipophilic drugs. Eur J Pharm Sci. 2005; 24:381–8.
  66. Porter CJH, Pouton CW, Culine JF, Charman WN. Enhancing intestinal drug solubilisation using lipid-based drug delivery systems. Adv Drug Deliv Rev. 2008; 60:673–91.
  67. Dahan A, Hoffman A. The effect of different lipid-based formulations on the oral absorption of lipophilic drugs: the ability of in vitro lipolysis and consecutive ex-vivo intestinal permeability data to predict in vivo bioavailability in rats. Eur J Pharm Biopharm. 2007; 67:96–105.
  68. Mercuri A, Passalacqua A, Wickham MJW. The effect of composition and gastric conditions on the self-emulsification process of ibuprofen-loaded self-emulsifying drug delivery systems: a microscopic and dynamic gastric model study. Pharm Res. 2011; 28:1540–51.
  69. Schaich KM, Shahidi F, Zhong Y, Eskin NAM. Lipid oxidation. In: Eskin NAM, Shahidi F, eds. Biochemistry of Foods, vol. 3. New York: Elsevier; 2013:419–78.
  70. Bowtle W. Materials, process, and manufacturing considerations for lipid-based hard-capsule formats. In: Hauss DJ, ed. Oral Lipid-Based Formulations Enhancing the Bioavailability of Poorly Water-Soluble Drugs. Vol. 170. New York: Informa Healthcare; 2007. p. 79–106.
  71. Khan AW, Kotta S, Ansari SH, et al. Potentials and challenges in self-nanoemulsifying drug delivery systems. Expert Opin Drug Deliv. 2012; 9:1305–17.
  72. Mahmoud EA, Bendas ER, Mohamed MI. Preparation and evaluation of self-nanoemulsifying tablets of carvedilol. AAPS PharmSciTech. 2009; 10:183–92.
  73. Huang Y, Tian R, Hu W, et al. A novel plug-controlled colon-specific pulsatile capsule with tablet of curcumin-loaded SMEDDS. Carbohydr Polym. 2012; 92:2218–23.
  74. Woo JS, Song YK, Hong JY, et al. Reduced food effect and enhanced bioavailability of a self-microemulsifying formulation of itraconazole in healthy volunteers. Eur J Pharm Sci. 2008; 33:59–65.
  75. Taha E, Ghorab D, Zaghloul AA. Bioavailability assessment of vitamin A self-nanoemulsified drug delivery systems in rats: a comparative study. Med Princ Pract. 2007; 16:355–9.
  76. Caliph SM, Charman WN, Porter CJ. Effect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats. J Pharm Sci. 2000; 89:1073–84.
  77. Sato K. Crystallization behaviour of fats and lipids – a review. Chem Eng Sci. 2001; 56:2255–65.
  78. Yao J, Zhu Y, Ren G, Hao W, Jin S. Development of a self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of curcumin. Drug Dev Ind Pharm. 2020;46(3):470–479.
  79. Porter CJ, Trevaskis NL, Charman WN. Lipid-based formulations: Optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231–248
  80. Zangenberg NH, Müllertz A, Kristensen HG, Hovgaard L. A dynamic in vitro lipolysis model: I. Controlling the rate of lipolysis by continuous addition of calcium. Eur J Pharm Sci. 2001;14(2):115–122
  81. Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying drug delivery systems: Preparation techniques and dosage forms. Drug Discov Today. 2008;13(13–14):606–612.
  82. Boyd BJ, Bergström CA. Viscosity and drug solubility in lipid-based formulations: Optimizing drug delivery. J Pharm Sci. 2011;100(8):2904–2908.
  83. Patil P, Joshi P, Paradkar A. Effect of formulation variables on preparation and evaluation of gelled self-emulsifying drug delivery system (SEDDS) of ketoprofen. AAPS PharmSciTech. 2004;5(3):E4
  84. Patil P, Joshi P, Paradkar A. Effect of formulation variables on preparation and evaluation of gelled self-emulsifying drug delivery system (SEDDS) of ketoprofen. AAPS PharmSciTech. 2004;5(3):E42
  85. Kommuru TR, Gurley B, Khan MA, Reddy IK. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: Formulation development and bioavailability assessment. Int J Pharm. 2001;212(2):233–246
  86. Boyd BJ, Bergström CA. Viscosity and drug solubility in lipid-based formulations: Optimizing drug delivery. J Pharm Sci. 2011;100(8):2904–2908.
  87. Shakeel F, Baboota S, Ahuja A, et al. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech. 2007;8(4):E104
  88. Porter CJ, Trevaskis NL, Charman WN. Lipid-based formulations: Optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231–248
  89. Patil P, Joshi P, Paradkar A. Effect of formulation variables on preparation and evaluation of gelled self-emulsifying drug delivery system (SEDDS) of ketoprofen. AAPS PharmSciTech. 2004;5(3):E42
  90. Kazi M, Al-Suwaidi A, Alanazi FK, et al. Enhancing oral bioavailability of apigenin using a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS): In vitro and in vivo evaluation. 2020;12(8):749
  91. Garg T, Singh O, Arora S, Murthy RS. Scaffold: A novel carrier for cell and drug delivery. Crit Rev Ther Drug Carrier Syst. 2012;29(1):1–63
  92. Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying drug delivery systems: Preparation techniques and dosage forms. Drug Discov Today. 2008;13(13–14):606–612.
  93. Khan AW, Kotta S, Ansari SH, Sharma RK, Ali J. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid naringenin: Design, characterization, in vitro and in vivo evaluation. Drug Deliv. 2015;22(4):552–561.
  94. Pouton CW, Porter CJ. Formulation of lipid-based delivery systems for oral administration: Materials, methods, and strategies. Adv Drug Deliv Rev. 2008;60(6):625–63
  95. Obaidat AA, Alzoubi NA, Sallam AS. Artificial intelligence in formulation design. Expert Opin Drug Deliv. 2020;17(6):849–861
  96. Patel J, Patel A, Raval M, Sheth N. Formulation strategies for drug delivery of tacrolimus: An overview. Int J Pharm Investig. 2012;2(4):169–176.
  97. Kalhapure RS, Suleman N, Mocktar C, et al. Nanoengineered drug delivery systems for enhancing antibiotic therapy. J Pharm Sci. 2015;104(3):872–905.
  98. Sharma P, Varma MV, Chawla HP, Panchagnula R. Lipid-based oral formulations for poorly water-soluble drugs: Enhancing bioavailability of anticancer drugs. Int J Pharm. 2004;275(1–2):53–66
  99. Bali V, Ali M, Ali J. Study of surfactant combinations and development of a novel nanoemulsion for minimizing variations in bioavailability of ezetimibe. Colloids Surf B Biointerfaces. 2010;76(2):410–420.
Special Issue Subscription Review Article
Volume 13
Special Issue 02
Received 05/12/2024
Accepted 16/01/2025
Published 29/01/2025
Publication Time 55 Days
216

Login


My IP

PlumX Metrics