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



Tavakoli N1 ; Varshosaz J1 ; Abbasi Niko M2
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences AND Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. School of Pharmacy and Pharmaceutical Sciences AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Isfahan Medical School Published:2013

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.
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