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

12 Citations (Scopus)

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

Fingerprint

Pharmacokinetics
Lipids
Biological Availability
Suspensions
Propylene Glycol
Water
Enzymes
Oleic Acid
Surface-Active Agents
Pharmaceutical Preparations
Solubility
Oral Administration
Stomach
Ethanol
antalarmin
cremophor EL

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Preformulation and pharmacokinetic studies on antalarmin : A novel stress inhibitor. / Sanghvi, Ritesh; Mogalian, Erik; Machatha, Stephen G.; Narazaki, Ryuichi; Karlage, Kelly L.; Jain, Parijat; Tabibi, S. Esmail; Glaze, Elizabeth; Myrdal, Paul B; Yalkowsky, Samuel H.

In: Journal of Pharmaceutical Sciences, Vol. 98, No. 1, 01.2009, p. 205-214.

Research output: Contribution to journalArticle

Sanghvi, R, Mogalian, E, Machatha, SG, Narazaki, R, Karlage, KL, Jain, P, Tabibi, SE, Glaze, E, Myrdal, PB & Yalkowsky, SH 2009, 'Preformulation and pharmacokinetic studies on antalarmin: A novel stress inhibitor', Journal of Pharmaceutical Sciences, vol. 98, no. 1, pp. 205-214. https://doi.org/10.1002/jps.21421
Sanghvi R, Mogalian E, Machatha SG, Narazaki R, Karlage KL, Jain P et al. Preformulation and pharmacokinetic studies on antalarmin: A novel stress inhibitor. Journal of Pharmaceutical Sciences. 2009 Jan;98(1):205-214. https://doi.org/10.1002/jps.21421
Sanghvi, Ritesh ; Mogalian, Erik ; Machatha, Stephen G. ; Narazaki, Ryuichi ; Karlage, Kelly L. ; Jain, Parijat ; Tabibi, S. Esmail ; Glaze, Elizabeth ; Myrdal, Paul B ; Yalkowsky, Samuel H. / Preformulation and pharmacokinetic studies on antalarmin : A novel stress inhibitor. In: Journal of Pharmaceutical Sciences. 2009 ; Vol. 98, No. 1. pp. 205-214.
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