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.

Drug Development and Industrial Pharmacy
Abeer M Al-GhananeemAftab Ansari

Abstract

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. TRAM-34 was successfully enteric microencapsulated by a coacervation method using the pH-sensitive Eudragit L 100 polymer. In this study, we utilized water-miscible 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. The resulting microparticles were spherical and uniform with an average particle size of 460 microm 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. The low oral bioavailability, even after enteric coating, could be attributed to the compound's inherent absorption...Continue Reading

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Citations

Sep 26, 2012·Drug Development and Industrial Pharmacy·Steffi ThomasCheng Shu Chaw
Nov 13, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christel A S BergströmAnette Mullertz
Apr 26, 2019·Annals of Clinical and Translational Neurology·Lee-Way JinIzumi Maezawa
Nov 19, 2013·Journal of Cellular and Molecular Medicine·Elizabeth A LogsdonFeilim Mac Gabhann

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