Journal of Thermal Analysis and Calorimetry

, Volume 123, Issue 3, pp 2157–2164 | Cite as

Effect of 70-kDa and 148-kDa dextran hydrogels on praziquantel solubility

  • Flávio dos Santos Campos
  • Laís Zuzzi Ferrari
  • Douglas Lopes Cassimiro
  • Clóvis Augusto Ribeiro
  • Adélia Emilia de Almeida
  • Maria Palmira Daflon Gremião


Praziquantel is an anthelmintic widely used in the treatment of schistosomiasis. Although a highly permeable drug, praziquantel is poorly soluble in water, limiting its bioavailability. Improving the solubility of poorly water-soluble drugs has become an important issue for analysis in pharmaceutical research. The use of dextran hydrogels is an advantageous strategy and the focus of extensive research. In this study, several hydrogels were developed from homologous polymer blends using 70 and 148 kDa dextrans in different proportions containing praziquantel, with the aim of evaluating the effects of polymeric release systems on the solubility of poorly water-soluble drugs such as praziquantel. Nine formulations were prepared, and the solubility of the drug incorporated was assessed. Three of the formations were selected to be characterized by DSC for the study in order to gain a better understanding of the thermal behavior of praziquantel incorporated into dextran hydrogels and the influence of polymers on the solubility of the drug, complemented by XRD and SEM techniques. According to the results, formation of crystallites of praziquantel occurred, probably due to the preparation procedures of the formulations, covering the surface of the polymer matrix and promoting a slight improvement in solubility. These data show that the use of hydrogels for the purposes of improving the solubility of poorly water-soluble drugs represents an effective strategy.


Praziquantel Dextran Homologous polymer blend Hydrogels Solubility Thermal analysis 



We would like to thank the LMA-IQ/UNESP from Araraquara for the FEG-SEM facilities.


  1. 1.
    Passerini N, Albertici B, Perissuti B, Rodriguez L. Evaluation of melt granulation and ultrasonic spray congealing as techniques to enhance the dissolution of praziquantel. Int J Pharm. 2006;318:92–102.CrossRefGoogle Scholar
  2. 2.
    Cioli D, Pica-Mattoccia L. Praziquantel. Parasitol Res. 2003;90:S3–9.Google Scholar
  3. 3.
    Souza ALR, Andreani T, Oliveira RN, Kill CP, Santos FK, Allegretti SM, Chaud MV, Souto EB, Silva AM, Gremião MPD. In vitro evaluation of permeation, toxicity and effect of praziquantel-loaded solid lipid nanoparticles against Schistosoma mansoni as a strategy to improve efficacy of the schistosomiasis treatment. Int J Pharm. 2014;463:31–7.CrossRefGoogle Scholar
  4. 4.
    Sadhu PS, Kumar SN, Chandrasekharam M, Pica-Mattoccia L, Cioli D, Rai VJ. Synthesis of new praziquantel analogues: potential candidates for the treatment of schistosomiasis. Bioorg Med Chem Lett. 2012;22:1103–6.CrossRefGoogle Scholar
  5. 5.
    Almeida AE, Souza ALR, Cassimiro DL, Gremião MPD, Ribeiro CA, Crespi MS. Thermal characterization of solid lipid nanoparticles containing praziquantel. J Therm Anal Calorim. 2012;108:333–9.CrossRefGoogle Scholar
  6. 6.
    Breda SA, Jimenez-Kairuruz AF, Manzo RH, Oliveira ME. Solubility behaviour and biopharmaceutical classification of novel high-solubility ciprofloxacin and norfloxacin pharmaceutical derivates. Inter Pharm. 2009;371:106–13.CrossRefGoogle Scholar
  7. 7.
    Chaud MV, Tamascia P, Lima AC, Paganelli MO, Gremião MPD, Freitas O. Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel. Braz J Pharm Sci. 2010;46:473–81.CrossRefGoogle Scholar
  8. 8.
    Leong KW, Langer R. Polymeric controlled drug delivery. Adv Drug Deliv Rev. 1987;1:199–233.CrossRefGoogle Scholar
  9. 9.
    Thakur RRS, McMillan HL, Jones DS. Solvent induced phase inversion-based in situ forming controlled release drug delivery implants. J Control Release. 2014;176:8–23.CrossRefGoogle Scholar
  10. 10.
    Kim S, Kim J, Jeon O, Kwon IC, Park K. Engineered polymers for advanced drug delivery. Eur J Pharm Biopharm. 2009;71:420–30.CrossRefGoogle Scholar
  11. 11.
    Alvarez-Lorenzo C, Blanco-Fernadez B, Puga AM, Concheiro A. Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. Adv Drug Deliv Ver. 2013;65:1148–71.CrossRefGoogle Scholar
  12. 12.
    Prezotti FG, Cury BSF, Evangelista RC. Mucoadhesive beads of gellan gum/pectin intended to controlled delivery of drugs. Carbohydr Polym. 2014;113:286–95.CrossRefGoogle Scholar
  13. 13.
    Petronijevic Z, Maluckov B, Smelcerovic A. Crosslinking of polysaccharides with activated dimethylsulfoxide. Tetrahedron Lett. 2014;54:3210–4.CrossRefGoogle Scholar
  14. 14.
    Mocanu G, Nichifor M. Cationic amphiphilic dextran hydrogels with potential biomedical applications. Carbohydr Polym. 2014;99:235–41.CrossRefGoogle Scholar
  15. 15.
    Cutiongco MFA, Tan MH, Ng MYK, Visage CL, Yim EKF. Composite pullulan-dextran polysaccharide scaffold with interfacial polyelectrolyte complexation fibers: a platform with enhanced cell interaction and spatial distribution. Acta Biomater. 2014;10:4410–8.CrossRefGoogle Scholar
  16. 16.
    Beloqui A, Solinís MA, Rieux A, Préat V, Rodríguez-Gascón A. Dextran-protamine coated nanostructured lipid carriers as mucus-penetrating nanoparticles for lipophilic drugs. Int J Pharm. 2014;468:105–11.CrossRefGoogle Scholar
  17. 17.
    Coviello T, Matricardi P, Marianecci C, Alhaique F. Polysaccharide hydrogels for modified release formulations. J Cont Release. 2007;119:5–24.CrossRefGoogle Scholar
  18. 18.
    Lloyd LL, Kennedy JF, Methacanon P, Paterson M, Knill CJ. Carbohydrate polymers as wound management aids. Carbohydr Polym. 1998;37:315–22.CrossRefGoogle Scholar
  19. 19.
    Hiemstra C, van der Aa LJ, Zhong Z, Dijkstra PJ, Feijen J. Novel in situ forming, degradable dextran hydrogels by Michael addition chemistry: synthesis, rheology, and degradation. Macromalecules. 2007;40:1165–73.CrossRefGoogle Scholar
  20. 20.
    Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev. 2012;64:49–60.CrossRefGoogle Scholar
  21. 21.
    Hamidi M, Azadi A, Rafiei P. Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev. 2008;60:1638–49.CrossRefGoogle Scholar
  22. 22.
    Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm. 2000;50:27–46.CrossRefGoogle Scholar
  23. 23.
    van Nostrum CF, Hennink WE. Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev. 2012;64:223–36.CrossRefGoogle Scholar
  24. 24.
    Hiemstra C, van der Aa LJ, Zhong Z, Dijkstra PJ, Feijen J. Rapidly in situ-forming degradable hydrogels from dextran thiols through Michael Addition. Biomacromalecules. 2007;8:1548–56.CrossRefGoogle Scholar
  25. 25.
    Chadha R, Bhandari S. Drug-excipient compatibility screening—role of thermoanalytical and spectroscopic techniques. J Pharm Biomed Anal. 2014;87:82–97.CrossRefGoogle Scholar
  26. 26.
    Nunes RS, Semaan FS, Riga AT, Cavalheiro ETG. Thermal behavior of verapamil hydrochloride and its association with excipients. J Therm Anal Calorim. 2009;97:349–53.CrossRefGoogle Scholar
  27. 27.
    Oliveira MA, Yoshida MI, Gomes ECL, Mussel WN, Viana-Soares VD, Pianetti GA. Análise Térmica aplicada à caracterização da sinvastatina em formulações farmacêuticas. Quim Nova. 2010;33:1653–7.CrossRefGoogle Scholar
  28. 28.
    Campos FS, Cassimiro DL, Crespi MS, Almeida AE, Gremião MPD. Preparation and characterization of Dextran-70 hydrogel for controlled release of praziquantel. Braz J Pharm Sci. 2013;49:75–83.CrossRefGoogle Scholar
  29. 29.
    Nepal PR, Han H, Choi H. Enhancement of solubility and dissolution of Coenzyme Q10 using solid dispersion formulation. Int J Pharm. 2010;383:147–53.CrossRefGoogle Scholar
  30. 30.
    Vippagunta SR, Maul KA, Tallavajhala S, Grant DJW. Solid-state characterization of nifedipine solid dispersions. Int Pharm. 2002;236:111–23.CrossRefGoogle Scholar
  31. 31.
    Abdullah M, Khairurrijal. Derivation of Scherrer relation using an approach in basic physics course. J Nanosains Nanotek. 2008;1:28–32.Google Scholar
  32. 32.
    Uvarov V, Popov I. Metrological characterization of X-ray diffraction methods at different acquisition geometries for determination of crystallite size in nano-scale materials. Mater Charact. 2013;85:111–23.CrossRefGoogle Scholar
  33. 33.
    Stenekes RJH, Talsma H, Hennink WE. Formulation of dextran hydrogel by crystallization. Biomaterials. 2001;22:1891–8.CrossRefGoogle Scholar
  34. 34.
    Zhang Y, Chu CC. Thermal and mechanical properties of biodegradable hydrophilic-hydrophobic hydrogels based on dextran and poly(lactic acid). J Mater Sci-Mater M. 2002;13:773–81.CrossRefGoogle Scholar
  35. 35.
    El-Subbagh HI, Al-Badr AA. Praziquantel. Anal. Prof Drug Subst and Exc. 1998;25:464–500.Google Scholar
  36. 36.
    Torre P, Torrado S, Torrado S. Preparation, dissolution and characterization of Praziquantel solid dispersion. Chem Pharm Bull. 1999;47:1629–33.CrossRefGoogle Scholar
  37. 37.
    Liu Y, Wang X, Wang JK, Ching CB. Structural characterization and enantioseparation of the chiral compound praziquantel. J Pharm Sci. 2004;39:3039–46.CrossRefGoogle Scholar
  38. 38.
    Mainardes RM, Gremião MPD, Evangelista RC. Thermoanalytical study of praziquantel loaded-PLGA nanoparticles. Rev Bras Ciênc Farm. 2006;42:523–30.CrossRefGoogle Scholar
  39. 39.
    Yuan W, Geng Y, Wu F, Liu Y, Guo M, Zhao H, Jin T. Preparation of polysaccharides glassy microparticles with stabilization of proteins. Int J Pharm. 2009;366:154–9.CrossRefGoogle Scholar
  40. 40.
    Cheng L, Lei L, Guo S. In vitro and in vivo evaluation of praziquantel loaded implants based on PEG/PCL blends. Int J Pharm. 2010;387:129–38.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2015

Authors and Affiliations

  • Flávio dos Santos Campos
    • 1
    • 3
  • Laís Zuzzi Ferrari
    • 1
  • Douglas Lopes Cassimiro
    • 2
  • Clóvis Augusto Ribeiro
    • 2
  • Adélia Emilia de Almeida
    • 1
  • Maria Palmira Daflon Gremião
    • 1
  1. 1.School of Pharmaceutical SciencesUNESP – Univ Estadual PaulistaAraraquaraBrazil
  2. 2.Institute of ChemistryUNESP – Univ Estadual PaulistaAraraquaraBrazil
  3. 3.Department of Drugs and Pharmaceuticals, School of Pharmaceutical SciencesSão Paulo State University – UNESPAraraquaraBrazil

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