AAPS PharmSciTech

, Volume 14, Issue 3, pp 919–926 | Cite as

Porous Starch: a Novel Carrier for Solubility Enhancement of Carbamazepine

  • Meer Tarique Ali
  • Ritesh Fule
  • Ajay Sav
  • Purnima Amin
Research Article


To circumvent the solubility-related issues associated with Biopharmaceutics Classification System class II drugs, a novel porous carrier has been developed. In the present study, a process for preparation of porous starch (PS) is demonstrated. The process briefly comprises of translucent gel preparation followed by solvent replacement, drying, and sizing. Carbamazepine (CBZ) was used as a drug candidate to exhibit solubility enhancement potential of PS. PS and CBZ-loaded PS (CBZ-PS) systems were characterized with respect to IR, DSC, XRD, SEM, and dissolution kinetic studies. PS-CBZ was found to follow a Fickian behavior during dissolution. In vivo studies conducted in mice displayed a superior performance of CBZ-PS as compared to neat CBZ.


carbamazepine dissolution solubility enhancement 



The authors would like to thank University Grants Commission, Government of India, for their financial support.


  1. 1.
    Hussain A, Rytting JH. Prodrug approach to enhancement of rate of dissolution of allopurinol. J Pharm Sci. 1974;63(5):798–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Alonzo DE, Gao Y, Zhou D, Mo H, Zhang GG, Taylor LS. Dissolution and precipitation behavior of amorphous solid dispersions. J Pharm Sci. 2011;100(8):3316–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Jadhav GS, Vavia PR. Physicochemical in silico and in-vivo evaluation of danazole-β cyclodextrin complex. Int J Pharm. 2008;2008(352):5–16.CrossRefGoogle Scholar
  4. 4.
    Ambrogi V, Perioli L, Pagano C, Marmottini F, Ricci M, Sagnella A, et al. Use of SBA-15 for furosemide oral delivery enhancement. Eur J Pharm Sci. 2012;46(1–2):43–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Tatavarti AS, Hoag SW. Microenvironmental pH modulation based release enhancement of a weakly basic drug from hydrophilic matrices. J Pharm Sci. 2006;95(7):1459–68.PubMedCrossRefGoogle Scholar
  6. 6.
    Murdande SB, Pikal MJ, Shanker RM, Bogner RH. Solubility advantage of amorphous pharmaceuticals: II. Application of quantitative thermodynamic relationships for prediction of solubility enhancement in structurally diverse insoluble pharmaceuticals. Pharm Res. 2010;27(12):2704–14.PubMedCrossRefGoogle Scholar
  7. 7.
    Meer TS, Sawant KP, Amin PD. Liquid anti solvent precipitation process for solubility modulation of bicalutamide. Acta Pharma. 2011;61(4):435–45.Google Scholar
  8. 8.
    Moffat AC, Osselton MD, Widdop Clarke B. Analysis of drugs and poisons, vol. II. London: Pharmaceutical Press; 2004. p. 747–49.Google Scholar
  9. 9.
    Ambrogi V, Perioli L, Marmottini F, Accorsi O, Pagano C, Ricci M, et al. Role of mesoporous silicates on carbamazepine dissolution rate enhancement. Microporous Mesoporous Mater. 2008;113(1–3):445–52.CrossRefGoogle Scholar
  10. 10.
    Achumecher GE. Therapeutic drug monitoring. New York: Appleton and Lange; 1995. p. 345–95.Google Scholar
  11. 11.
    Tayel SA, Soliman II, Louis D. Improvement of dissolution properties of carbamazepine through application of liquisolid tablet technique. Eur J Pharm Biopharm. 2008;69(1):342–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Wang Z, Chen B, Quan G, Li F, Wu Q, Dian L, et al. Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica. Int J Nanomedicine. 2012;7(1):5807–18.PubMedGoogle Scholar
  13. 13.
    Wang M, Rutledge GC, Myerson AS, Trout BL. Production and characterization of carbamazepine nanocrystals by electrospraying for continuous pharmaceutical manufacturing. J Pharm Sci. 2012;101(3):1178–88.PubMedCrossRefGoogle Scholar
  14. 14.
    Xu L, Ming L, Zhefei G, Lin H, Xin F, Chuanbin W. Improving the chemical stability of amorphous solid dispersion with cocrystal technique by hot melt extrusion. Pharm Res. 2012;29(3):806–17.CrossRefGoogle Scholar
  15. 15.
    Rowe RC, Shesky PJ, Quinn ME. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical Press; 2009. p. 685–90.Google Scholar
  16. 16.
    Uthumporn U, Zaidul ISM, Karim AA. Hydrolysis of granular starch at sub-gelatinization temperature using a mixture of amylolytic enzymes. Food Bioprod Process. 2010;88(1):47–54.CrossRefGoogle Scholar
  17. 17.
    Guan JJ, Hanna MA. Extruding foams from corn starch acetate and native corn starch. Biomacromolecules. 2004;5(6):2329–39.PubMedCrossRefGoogle Scholar
  18. 18.
    Torres FG, Boccaccini AR, Troncoso OP. Microwave processing of starch based porous structures for tissue engineering scaffolds. J Appl Polym Sci. 2007;103(2):1332–9.CrossRefGoogle Scholar
  19. 19.
    Manoi K, Rizvi SSH. Physicochemical characteristics of phosphorylated cross-linked starch produced by reactive supercritical fluid extrusion. Carbohydr Polym. 2010;81(3):687–94.CrossRefGoogle Scholar
  20. 20.
    Wu C, Wang Z, Zhi Z, Jiang T, Zhang J, Wang S. Development of biodegradable porous starch foam for improving oral delivery of poorly water soluble drugs. Int J Pharm. 2011;403(1–2):162–9.PubMedCrossRefGoogle Scholar
  21. 21.
    The United States Pharmacopeia (USP29). 29th ed. Rockville, MD: United States Pharmacopeial Convention Inc.; 2006.Google Scholar
  22. 22.
    Ahuja N, Katare OP, Singh B. Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers. Eur J Pharm Biopharm. 2007;65(1):26–38.PubMedCrossRefGoogle Scholar
  23. 23.
    Korsemeyer RW, Gurney R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25–35.CrossRefGoogle Scholar
  24. 24.
    Grzesiak AL, Lang M, Kim K, Matzger AJ. Comparison of the four anhydrous polymorphs of carbamazepine and the crystal structure of form I. J Pharm Sci. 2003;92(11):2260–71.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang B, Cui D, Liu M, Gong H, Huang Y, Han F. Corn porous starch: preparation, characterization and adsorption property. Int J Biol Macromol. 2012;50(1):250–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Vasko PD, Blackwell J, KoenigInfrared JL. Raman spectroscopy of carbohydrates: part II: normal coordinate analysis of α-D-glucose. Carbohydr Res. 1972;23(3):407–16.CrossRefGoogle Scholar
  27. 27.
    Cael SJ, Koenig JL, Blackwell J. Infrared and Raman spectroscopy of carbohydrates: part III: Raman spectra of the polymorphic forms of amylose. Carbohydr Res. 1973;29(1):123–34.PubMedCrossRefGoogle Scholar
  28. 28.
    Dinunzio JC, Miller DA, Yang W, Mcginity GW, Williams RO. Amorphous compositions using concentration enhancing polymers for improved bioavailability of itraconazole. Mol Pharm. 2008;5(6):968–80.PubMedCrossRefGoogle Scholar
  29. 29.
    Chan L, Caixia L, Yuan L, Jian-Feng C. Formation of bicalutamide nanodispersion for dissolution rate enhancement. Int J Pharm. 2011;404(1–2):257–63.Google Scholar
  30. 30.
    Corrigan OI, Holohan EM. Amorphous spray-dried hydroflumethiazide-polyvinylpyrrolidone systems: physicochemical properties. J Pharm Pharmacol. 1984;36(4):217–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Clinckers R, Smolders I, Meurs A, Ebinger G, Michotte Y. Quantitative in vivo microdialysis study on the influence of multidrug transporters on the blood–brain barrier passage of oxcarbazepine: concomitant use of hippocampal monoamines as pharmacodynamic markers for the anticonvulsant activity. J Pharmacol Exp Ther. 2005;314(2):725–31.PubMedCrossRefGoogle Scholar
  32. 32.
    Hoogerkamp A, Vis PW, Danhof M, Voskuyl RA. Characterization of the pharmacodynamics of several antiepileptic drugs in a direct cortical stimulation model of anticonvulsant effect in the rat. J Pharmacol Exp Ther. 1994;269(2):521–8.PubMedGoogle Scholar
  33. 33.
    Paschoa OED, Mandema JW, Voskuyl RA, Danhof M. Pharmacokinetic-pharmacodynamic modeling of the anticonvulsant and electroencephalogram effects of phenytoin in rats. J Pharmacol Exp Ther. 1998;284(2):460–6.PubMedGoogle Scholar
  34. 34.
    Qian D, Chang PR, Ma X. Preparation of controllable porous starch with different starch concentrations by the single or dual freezing process. Carbohydr Polym. 2011;86(3):1181–6.CrossRefGoogle Scholar
  35. 35.
    Qian D, Anderson DP, Ma X. Preparation and properties of the succinic ester of porous starch. Carbohydr Polym. 2012;88(2):604–8.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Meer Tarique Ali
    • 1
  • Ritesh Fule
    • 1
  • Ajay Sav
    • 1
  • Purnima Amin
    • 1
  1. 1.Department of Pharmaceutical Sciences and TechnologyInstitute of Chemical TechnologyMumbaiIndia

Personalised recommendations