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 Citations (Scopus)

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

Fingerprint

Microencapsulation
Drug Compounding
Dosage Forms
Drug Discovery
Immunosuppressive Agents
Derivatives
Biological Availability
Coatings
Acetone
Macaca mulatta
Drug delivery
Encapsulation
Particle Size
Organic solvents
Oral Administration
Hydrolysis
Polymers
Ethanol
Particle size
Alcohols

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Organic Chemistry

Cite this

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

In: Drug Development and Industrial Pharmacy, Vol. 36, No. 5, 05.2010, p. 563-569.

Research output: Contribution to journalArticle

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