Preformulation and pharmacokinetic studies on antalarmin: A novel stress inhibitor

Ritesh Sanghvi, Erik Mogalian, Stephen G. Machatha, Ryuichi Narazaki, Kelly L. Karlage, Parijat Jain, S. Esmail Tabibi, Elizabeth Glaze, Paul B. Myrdal, Samuel H. Yalkowsky

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The preformulation, solubilization and pharmacokinetic evaluation of antalarmin, a stress inhibitor, have been conducted. Antalarmin has a poor water solubility of less than 1 μg/mL and is weakly basic with an experimentally determined pKa of 5.0. Multiple solubilization approaches including pH-control either alone or in combination with cosolvents, surfactants and complexing agents have been investigated. The applicability of lipid-based systems has also been explored. Four formulations, each with a targeted drug loading capacity of 100 mg/mL, show potential for oral administration. Three of these formulations are aqueous solutions (10% ethanol + 40% propylene glycol; 20% cremophor EL; 20% sulfobutylether-β-cyelodex-trin) each buffered at pH 1. The fourth formulation is a lipid-based formulation comprising of 20% oleic acid, 40% cremophor EL and 40% Labrasol. No precipitation was observed following dilution of the four formulations with water and enzyme free simulated gastric fluid. However, only the lipid-based formulation successfully resisted drug precipitation following dilution with enzyme free simulated intestinal fluid. Pharmacokinetic analysis conducted in rats revealed that the 20% cremophor EL solution formulation has a fivefold higher oral bioavailability compared to a suspension formulation. The lipid-based formulation resulted in over 12-fold higher bioavailability as compared to the suspension formulation, the highest amongst the formulations examined.

Original languageEnglish (US)
Pages (from-to)205-214
Number of pages10
JournalJournal of pharmaceutical sciences
Volume98
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Antalarmin
  • Complexing agents
  • Cosolvent
  • Lipid-based formulation
  • Solubility
  • Surfactant

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Preformulation and pharmacokinetic studies on antalarmin: A novel stress inhibitor'. Together they form a unique fingerprint.

  • Cite this

    Sanghvi, R., Mogalian, E., Machatha, S. G., Narazaki, R., Karlage, K. L., Jain, P., Tabibi, S. E., Glaze, E., Myrdal, P. B., & Yalkowsky, S. H. (2009). Preformulation and pharmacokinetic studies on antalarmin: A novel stress inhibitor. Journal of pharmaceutical sciences, 98(1), 205-214. https://doi.org/10.1002/jps.21421