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 language | English (US) |
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Pages (from-to) | 563-569 |
Number of pages | 7 |
Journal | Drug Development and Industrial Pharmacy |
Volume | 36 |
Issue number | 5 |
DOIs | |
State | Published - May 2010 |
Keywords
- Bioavailability
- Coacervation
- Enteric coating
- Microencapsulation
- Oral
- TRAM-34
ASJC Scopus subject areas
- Drug Discovery
- Pharmacology
- Organic Chemistry