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Optimization of metronidazole sustained-release films using D-optimal design.

Abstract
The aim of this study was to develop sustained-release metronidazole films for periodontal pockets using a computer-aided statistical approach. The studied independent variables were the amount of polycaprolactone, metronidazole, hydroxypropylmethyl cellulose and glyceryl monostearate. The response of interest was the cumulative percentage release of metronidazole at 1, 2, 3, 4 and 5 days. The films were prepared using a melt method. The physicochemical properties and release profiles of the films were investigated. Model validation was also performed. The produced films were thin white sheets with a smooth and glossy surface. Each sheet had an average weight of 9.31 ± 0.10mg. The metronidazole was uniformly dispersed in the film, and the percentage of drug loading was 100.12 ± 4.38%. The thickness of the film was 325 ± 5.27 μm. The puncture strength, % elongation and Young's modulus were 11.58 ± 0.51 N/mm(2), 33.51 ± 3.61%, and 0.347 ± 0.02 1N/mm(2), respectively. The actual drug release profiles of the optimal formulation films were close to the predicted responses. Metronidazole was slowly released from the matrices over a period of at least 5 days. The release mechanism of the films followed Fickian diffusion. This study demonstrates that appropriate D-optimal design and optimization techniques can be successfully used in the development of metronidazole sustained-release films.
AuthorsJomjai Peerapattana, Teeraphat Ngamsupsiri, Nopadol Cheucharoenvasuchai, Charnnarong Saikaew
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 484 Issue 1-2 Pg. 1-7 (Apr 30 2015) ISSN: 1873-3476 [Electronic] Netherlands
PMID25681726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Infective Agents
  • Delayed-Action Preparations
  • Metronidazole
Topics
  • Anti-Infective Agents (chemistry, pharmacokinetics)
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations (chemistry, pharmacokinetics)
  • Drug Delivery Systems (methods)
  • Drug Design
  • Metronidazole (chemistry, pharmacokinetics)

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