Methodology for replacing dipolar aprotic solvents used in API processing with safe hydrogen-bond donor and acceptor solvent-pair mixtures

Alif Duereh, Yoshiyuki Sato, Richard Lee Smith, Hiroshi Inomata

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A methodology is presented that allows hazardous dipolar aprotic solvents used in the pharmaceutical processing industries to be replaced with solvent-pair mixtures that consist of a hydrogen-bond donor (HBD) solvent and a hydrogen-bond acceptor (HBA) solvent. The methodology uses the solubility of the active pharmaceutical ingredient (API) in hazardous solvents to estimate the range of required solubility parameters and Kamlet.Taft parameters for the API and then intersects these ranges with the solubility parameters and Kamlet.Taft parameters of the solvent-pair mixtures to identify favorable solvent pairs and possible working compositions. Solvent pairs are ranked according to GSK safety and health scores. The methodology was applied to 13 APIs, where it was found that nonaqueous mixtures (ethanol.isopropyl acetate, ethanol.ethyl acetate, and ethanol.butyl acetate) and aqueous mixtures (water-γ-valerolactone and water.dimethyl sulfoxide) are highly ranked and applicable to many APIs. Solvent pairs were eliminated from consideration due to their inability to simultaneously satisfy Kamlet.Taft acidity, basicity, and polarity parameter constraints. The proposed methodology makes it simple to identify and rank HBD.HBA solvent-pair mixtures for replacement of dipolar aprotic solvents used in the pharmaceutical processing industries.

Original languageEnglish
Pages (from-to)114-124
Number of pages11
JournalOrganic Process Research and Development
Volume21
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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