AAPS PharmSciTech

, Volume 19, Issue 5, pp 2288–2300 | Cite as

Application of Solvent Parameters for Predicting Organogel Formation

  • Beibei Hu
  • Wei Sun
  • Baixue Yang
  • Heran Li
  • Liuchenzi Zhou
  • Sanming LiEmail author
Research Article


Solvents, accounting the majority of the organogel system, have a tremendous impact on the characteristics of gels. To date, there is a large variety of organogel systems; relatively few have been investigated in the field of structure-solvent correlation. Here, a series of solvent parameters were applied to explore the role of solvent effect on network forming and gel property, intending to build the connection between the precise solvent parameter and gel property. Among the solvent parameters, Kamlet–Taft Parameters and Hansen solubility parameters can distinguish specific types of intermolecular interactions, which could correlate solvent parameter with the gel property. From an analysis of the morphologies obtained from POM and SEM, the gelator structure has an impact on its self-assembly. For possible conformations, the gelators were investigated through XRD. The investigation of solvent-property relationship will provide a theoretical basis for controllable drug delivery implants.


solvent parameter Hansen solubility parameters gelation organogels 


Funding Information

This work was supported by National Natural Science Foundation of China under Grant No. 81273445.

Supplementary material

12249_2018_1074_MOESM1_ESM.docx (974 kb)
ESM 1 (DOCX 973 kb)


  1. 1.
    Loh XJ, Nam Nguyen VP, Kuo N, Li J. Encapsulation of basic fibroblast growth factor in thermogelling copolymers preserves its bioactivity. J Mater Chem. 2011;21(7):2246.CrossRefGoogle Scholar
  2. 2.
    Kharkar PM, Kiick KL, Kloxin AM. Designing degradable hydrogels for orthogonal control of cell microenvironments. Chem Soc Rev. 2013;42(17):7335–72.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Han L, Xu J, Lu X, Gan D, Wang Z, Wang K, et al. Biohybrid methacrylated gelatin/polyacrylamide hydrogels for cartilage repair. J Mater Chem B. 2017;5(4):731–41.CrossRefGoogle Scholar
  4. 4.
    Deng J, Cheng C, Teng Y, Nie C, Zhao C. Mussel-inspired post-heparinization of a stretchable hollow hydrogel tube and its potential application as an artificial blood vessel. Polym Chem. 2017;8(14):2266–75.CrossRefGoogle Scholar
  5. 5.
    Liu Y, Yang F, Feng L, Yang L, Chen L, Wei G, et al. In vivo retention of poloxamer-based in situ hydrogels for vaginal application in mouse and rat models. Acta Pharm Sin B. 2017;7(4):502–9.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Vintiloiu A, Leroux JC. Organogels and their use in drug delivery—a review. J Control Release. 2008;125(3):179–92.CrossRefPubMedGoogle Scholar
  7. 7.
    Sangeetha NM, Maitra U. Supramolecular gels: functions and uses. Chem Soc Rev. 2005;34(10):821–36.CrossRefPubMedGoogle Scholar
  8. 8.
    Ye F, Chen S, Tang G, Ma M, Wang X. Self-assembled nanofibrillar gel network toughened PMMA nanocomposite by in situ thermal polymerization of MMA gel. Colloid Surface A. 2015;480:1–10.CrossRefGoogle Scholar
  9. 9.
    Liow SS, Karim AA, Loh XJ. Biodegradable thermogelling polymers for biomedical applications. MRS Bull. 2016;41(07):557–66.CrossRefGoogle Scholar
  10. 10.
    Lupi FR, Greco V, Baldino N, de Cindio B, Fischer P, Gabriele D. The effects of intermolecular interactions on the physical properties of organogels in edible oils. J Colloid Interface Sci. 2016;483:154–64.CrossRefPubMedGoogle Scholar
  11. 11.
    Huang C-B, Chen L-J, Huang J, Xu L. A novel pyrene-containing fluorescent organogel derived from a quinoline-based fluorescent porbe: synthesis, sensing properties, and its aggregation behavior. RSC Adv. 2014;4(37):19538.CrossRefGoogle Scholar
  12. 12.
    Pirner D, Dulle M, Mauer MEJ, Förster S. Reinforcement of nanostructured organogels by hydrogen bonds. RSC Adv. 2016;6(48):42730–8.CrossRefGoogle Scholar
  13. 13.
    Simsolo EE, Eroglu I, Tanriverdi ST, Ozer O. Formulation and evaluation of organogels containing hyaluronan microparticles for topical delivery of caffeine. AAPS PharmSciTech. 2018;19(3):1367–76.PubMedGoogle Scholar
  14. 14.
    Uzan S, Barış D, Çolak M, Aydın H, Hoşgören H. Organogels as novel carriers for dermal and topical drug delivery vehicles. Tetrahedron. 2016;72(47):7517–25.CrossRefGoogle Scholar
  15. 15.
    Mandal D, Mandal SK, Ghosh M, Das PK. Phenylboronic acid appended pyrene-based low-molecular-weight injectable hydrogel: glucose-stimulated insulin release. Chem Eur J. 2015;21(34):12042–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhao Y, Zhou L, Liu J, Chen Z, Yang L, Shi H. Preparation and investigation of a novel levobupivacaine in situ implant gel for prolonged local anesthetics. Artif Cells Nanomed Biotechnol. 2017;45(3):404–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Li Z, Cao J, Li H, Liu H, Han F, Liu Z, et al. Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation. Drug Deliv. 2016;23(8):3168–78.CrossRefPubMedGoogle Scholar
  18. 18.
    Hu B, Wang W, Wang Y, Yang Y, Xu L, Li S. Degradation of glutamate-based organogels for biodegradable implants: in vitro study and in vivo observation. Mater Sci Eng C Mater Biol Appl. 2018;82:80–90.CrossRefPubMedGoogle Scholar
  19. 19.
    Long D, Gong T, Zhang Z, Ding R, Fu Y. Preparation and evaluation of a phospholipid-based injectable gel for the long term delivery of leuprolide acetaterrh. Acta Pharm Sin B. 2016;6(4):329–35.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Martin B, Brouillet F, Franceschi S, Perez E. Evaluation of organogel nanoparticles as drug delivery system for lipophilic compounds. AAPS PharmSciTech. 2017;18(4):1261–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Gravelle AJ, Davidovich-Pinhas M, Zetzl AK, Barbut S, Marangoni AG. Influence of solvent quality on the mechanical strength of ethylcellulose oleogels. Carbohydr Polym. 2016;135:169–79.CrossRefPubMedGoogle Scholar
  22. 22.
    Liu C, Corradini M, Rogers MA. Self-assembly of 12-hydroxystearic acid molecular gels in mixed solvent systems rationalized using Hansen solubility parameters. Colloid Polym Sci. 2015;293(3):975–83.CrossRefGoogle Scholar
  23. 23.
    Lan Y, Corradini MG, Weiss RG, Raghavan SR, Rogers MA. To gel or not to gel: correlating molecular gelation with solvent parameters. Chem Soc Rev. 2015;44(17):6035–58.CrossRefPubMedGoogle Scholar
  24. 24.
    Haldar S, Karmakar K. A systematic understanding of gelation self-assembly: solvophobically assisted supramolecular gelation via conformational reorientation across amide functionality on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid). RSC Adv. 2015;5(81):66339–54.CrossRefGoogle Scholar
  25. 25.
    Zhao C, Wang H, Bai B, Qu S, Song J, Ran X, et al. Organogels from unsymmetrical [small pi]-conjugated 1,3,4-oxadiazole derivatives. New J Chem. 2013;37(5):1454–60.CrossRefGoogle Scholar
  26. 26.
    Edwards W, Smith DK. Dynamic evolving two-component supramolecular gels—hierarchical control over component selection in complex mixtures. J Am Chem Soc. 2013;135(15):5911–20.CrossRefPubMedGoogle Scholar
  27. 27.
    Bustamante P, Navarro-Lupión J, Peña MA, Escalera B. Hildebrand solubility parameter to predict drug release from hydroxypropyl methylcellulose gels. Int J Pharm. 2011;414(1):125–30.CrossRefPubMedGoogle Scholar
  28. 28.
    Bonnet J, Suissa G, Raynal M, Bouteiller L. Organogel formation rationalized by Hansen solubility parameters: dos and don’ts. Soft Matter. 2014;10(18):3154–60.CrossRefPubMedGoogle Scholar
  29. 29.
    Bonnet J, Suissa G, Raynal M, Bouteiller L. Organogel formation rationalized by Hansen solubility parameters: influence of gelator structure. Soft Matter. 2015;11(11):2308–12.CrossRefPubMedGoogle Scholar
  30. 30.
    Diehn KK, Oh H, Hashemipour R, Weiss RG, Raghavan SR. Insights into organogelation and its kinetics from Hansen solubility parameters. Toward a priori predictions of molecular gelation. Soft Matter. 2014;10(15):2632–40.CrossRefPubMedGoogle Scholar
  31. 31.
    Chen S, Tang G, Wu B, Ma M, Wang X. The key effect of the self-assembly mechanism of dendritic gelators: solubility parameters, generations and terminal effects. RSC Adv. 2015;5(44):35282–90.CrossRefGoogle Scholar
  32. 32.
    Vay K, Scheler S, Frieß W. Application of Hansen solubility parameters for understanding and prediction of drug distribution in microspheres. Int J Pharm. 2011;416(1):202–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Gårdebjer S, Andersson M, Engström J, Restorp P, Persson M, Larsson A. Using Hansen solubility parameters to predict the dispersion of nano-particles in polymeric films. Polym Chem. 2016;7(9):1756–64.CrossRefGoogle Scholar
  34. 34.
    Wang K, Jia Q, Han F, Liu H, Li S. Self-assembled L-alanine derivative organogel as in situ drug delivery implant: characterization, biodegradability, and biocompatibility. Drug Dev Ind Pharm. 2010;36(12):1511–21.CrossRefPubMedGoogle Scholar
  35. 35.
    Wang K, Jia Q, Yuan J, Li S. A novel, simple method to simulate gelling process of injectable biodegradable in situ forming drug delivery system based on determination of electrical conductivity. Int J Pharm. 2011;404(1–2):176–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Li Z, Cao J, Hu B, Li H, Liu H, Han F, et al. Studies on the in vitro and in vivo degradation behavior of amino acid derivative-based organogels. Drug Dev Ind Pharm. 2016;42(11):1732–41.CrossRefPubMedGoogle Scholar
  37. 37.
    Bielejewski M, Kowalczuk J, Kaszynska J, Lapinski A, Luboradzki R, Demchuk O, et al. Novel supramolecular organogels based on a hydrazide derivative: non-polar solvent-assisted self-assembly, selective gelation properties, nanostructure, solvent dynamics. Soft Matter. 2013;9(31):7501–14.CrossRefGoogle Scholar
  38. 38.
    Edwards W, Lagadec CA, Smith DK. Solvent–gelator interactions—using empirical solvent parameters to better understand the self-assembly of gel-phase materials. Soft Matter. 2011;7(1):110–7.CrossRefGoogle Scholar
  39. 39.
    Hansen CM. Hansen solubility parameters: a user’s handbook. Milton Park: Taylor & Francis Group; 2007.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Beibei Hu
    • 1
  • Wei Sun
    • 1
  • Baixue Yang
    • 1
  • Heran Li
    • 1
  • Liuchenzi Zhou
    • 1
  • Sanming Li
    • 1
    Email author
  1. 1.School of PharmacyShenyang Pharmaceutical UniversityBenxiPeople’s Republic of China

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