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

Abeer M. Al-Ghananeem, Maggie Abbassi, Srishti Shrestha, Girija Raman, Heike Wulff, Lara Pereira, Aftab Ansari

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)563-569
Number of pages7
JournalDrug Development and Industrial Pharmacy
Volume36
Issue number5
DOIs
StatePublished - May 2010

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Keywords

  • Bioavailability
  • Coacervation
  • Enteric coating
  • Microencapsulation
  • Oral
  • TRAM-34

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Organic Chemistry

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