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Author Notes:

Correspondence to: Abeer Al-Ghananeem, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082. Phone: 859 257 4032, Fax: 859 257 7585, amalg0@email.uky.edu.

Subjects:

Research Funding:

This work was supported by RO1-GM076063 to HW with a subcontract to AMA.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Chemistry, Medicinal
  • Pharmacology & Pharmacy
  • Bioavailability
  • coacervation
  • enteric coating
  • microencapsulation
  • oral
  • TRAM-34
  • K+ CHANNEL
  • MICROPARTICLES
  • IKCA1
  • CELLS

Formulation-based approach to support early drug discovery and development efforts: a case study with enteric microencapsulation dosage form development for a triarylmethane derivative TRAM-34; a novel potential immunosuppressant

Tools:

Journal Title:

Drug Development and Industrial Pharmacy

Volume:

Volume 36, Number 5

Publisher:

, Pages 563-569

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: Enteric microencapsulation of the potential immunosuppressant TRAM-34 was investigated as a means of enhancing oral drug delivery and minimizing or eliminating hydrolysis of pyrazole-substituted triarylmethane to the respective alcohol. Method: TRAM-34 was successfully enteric microencapsulated by a coacervation method using the pH-sensitive Eudragit L 100 polymer. In this study, we utilized watermiscible organic solvents such as acetone and ethanol, which are considered safe class 3 solvents according to the ICH guideline. We deemed such an approach suitable for safe scale up and for enteric coating application to other compounds of a similar lipophilicity. Results: The resulting microparticles were spherical and uniform with an average particle size of 460 μm at 15 theoretical loading. The encapsulation efficiency was 90 ± 1.9 and the percentage yield was found to be 91.5 ± 0.3. The oral administration in rhesus macaques of TRAM-34-loaded enteric-coated microparticles illustrated six times enhancement in its oral bioavailability. However, the TRAM-34 plasma concentration was less than the therapeutic effective level. Conclusion: The low oral bioavailability, even after enteric coating, could be attributed to the compound's inherent absorption characteristics and high lipophilicity.

Copyright information:

© 2010 Informa UK, Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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