Effects of Concentration, Temperature and Polymer Type on Drug Release from Montmorillonite-Donepezil Nanocomposites

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences AND Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Professor, Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences AND Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Student of Pharmacy, School of Pharmacy and Pharmaceutical Sciences AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Donepezil (DON) is a reversible and non-competitive cholinesterase inhibitor and a well-known drug for treatment of Alzheimer’s disease. The main objective of this study was to prepare an oral dosage form of DON with gradual drug release characteristics in order to reduce the gastrointestinal side effects and increase patient compliance. For this purpose DON was intercalated into montmorillonite (MMT) and drug release was manipulated by inclusion of different polymers into DON-MMT hybrids.Methods: DON-MMT hybrids were prepared and the effects of drug concentration and temperature on drug loading were evaluated. To achieve the desired release profile, DON-MMT hybrids were dispersed separately into a solution of carbomer, chitosan, sodium alginate, or Eudragit. The resultant suspensions were spray-dried separately. The weight fraction of hybrid to the polymers was 1.0:1.0, 1.0:0.6, and 1.0:0.3. All prepared nanocomposites were tested for drug loading capacity and drug release profiles. The surface morphology of optimized nanoparticles was analyzed by scanning electron microscopy.Findings: The highest drug loading (16.8%) was achieved by nanocomposites containing 2 mM DON prepared at 70°C (formulation coded D2MMT70). The lowest drug loading (12.3%) belonged to hybrids coded D1MMT25 prepared at 25°C. Among four polymers, Eudragit L100-55 and sodium alginate had more distinct effect than carbomer or chitosan on drug release from the DON-MMT hybrids. Cumulative drug release from nanocomposites coded as H1AL1 was 34.0% and 18.84% in hydrochloric acid and phosphate buffer, respectively.Conclusion: Increasing temperature to 70°C could increase drug loading during the preparation of hybrids. Drug release rate from hybrids could be certainly manipulated by the presence of sodium alginate or Eudragit L100-55.

Keywords

References

  1. Stahl SM. The new cholinesterase inhibitors for Alzheimer's disease, Part 2: illustrating their mechanisms of action. J Clin Psychiatry 2000; 61(11): 813-4.
  2. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 2006; (1): CD005593.
  3. Banker GS, Siepmann J, Rhodes CT. Modern pharmaceutics. 4th ed. New York, NY: 2002. p. 501-27.
  4. Gennaro AR. Remington, the science and practice of pharmacy. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000. p.1660-3.
  5. Aulton ME, Taylor KMG. Pharmaceutics: The science of dosage form design. 2nd ed. Edinburgh, UK: Churchill Livingstone; 2001. p. 290-1, 413-8.
  6. Park JK, Choy YB, Oh JM, Kim JY, Hwang SJ, Choy JH. Controlled release of donepezil intercalated in smectite clays. Int J Pharm 2008; 359(1-2): 198-204.
  7. Haddadi Asl V. Principles of polymerization engineering. 1st ed. Tehran, Iran: Tehran Polytechnic Press; 2001. p. 619-22.
  8. Dong Y, Feng SS. Poly (d,l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs. Biomaterials 2005; 26(30): 6068-76.
  9. Feng SS, Mei L, Anitha P, Gan CW, Zhou W. Poly(lactide)-vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel. Biomaterials 2009; 30(19): 3297-306.
  10. Depan D, Kumar AP, Singh RP. Cell proliferation and controlled drug release studies of nanohybrids based on chitosan-g-lactic acid and montmorillonite. Acta Biomater 2009; 5(1): 93-100.
  11. Lee Y, Kuo T, Chen B, Feng Y, Wen Y, Lin W, et al. Toxicity assessment of montmorillonite as a drug carrier for pharmaceutical applications: yeast and rats model. Biomed Engin Appl, Basis and Communications 2005; 17(2): 12-8.
  12. Rowe RC, Sheskey PJ, Weller PJ. Handbook of pharmaceutical excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003. p. 89,132, 464, 543.
  13. Ansel HC, Allen LVJ, Popovich NG. Pharmaceutical dosage forms and drug delivery systems. 8th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005.
  14. Joshi GV, Kevadiya BD, Patel HA, Bajaj HC, Jasra RV. Montmorillonite as a drug delivery system: intercalation and in vitro release of timolol maleate. Int J Pharm 2009; 374(1-2): 53-7.
  15. Kevadiya BD, Joshi GV, Bajaj HC. Layered bionanocomposites as carrier for procainamide. Int J Pharm 2010; 388(1-2): 280-6.
  16. Hua S, Yang H, Wang A. A pH-sensitive nanocomposite microsphere based on chitosan and montmorillonite with in vitro reduction of the burst release effect. Drug Dev Ind Pharm 2010; 36(9): 1106-14.
  17. Chen F, Zhang ZR, Yuan F, Qin X, Wang M, Huang Y. In vitro and in vivo study of N-trimethyl chitosan nanoparticles for oral protein delivery. Int J Pharm 2008; 349(1-2): 226-33.
  18. Soundrapandian C, Sa B, Datta S. Organic-inorganic composites for bone drug delivery. AAPS PharmSciTech 2009; 10(4): 1158-71.
Journal of Isfahan Medical School
Volume 31, Issue 225 - Serial Number 225
January and February 2013
Pages 92-103

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History

  • Receive Date: 09 December 2012
  • Revise Date:
  • Accept Date: 06 April 2022

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