Green Technology for Salt Formation: Slurry Reactive Crystallization Studies for Papaverine HCl and 1:1 Haloperidol-Maleic Acid Salt

Jeanne Dewi Damayanti, Dhanang Edy Pratama, Tu Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Papaverine HCl was successfully suspended by slurry reactive crystallization with the use of isopropyl alcohol (IPA) at 25 °C, a solid-to-liquid ratio of 0.19 g/mL, an aging time of 8 h, a yield of 82.0 w/w %, crystal sizes of 200-400 μm, and the value for enthalpy of fusion of 154.5 J/g. The poor solubility of papaverine in IPA and better solubility of papaverine HCl in water-containing IPA had made the homogeneous nucleation of papaverine HCl dominate. Crystal size and crystallinity of papaverine HCl were time and temperature dependent. However, the 1:1 haloperidol-maleic acid salt was also successfully suspended and generated by slurry reactive crystallization with the use of water at 25 °C, a solid-to-liquid ratio of 0.18 g/mL, an aging time of 8 h, a yield of 82.0 w/w %, crystal sizes of 500-1000 μm, and the value for enthalpy of fusion of 84.9 J/g. The poor solubility of haloperidol and 1:1 haloperidol-maleic acid salt in water had made the heterogeneous nucleation of 1:1 haloperidol-maleic acid salt dominate. Crystal size and crystallinity of 1:1 haloperidol-maleic acid salt became less sensitive to time and temperature. Comparing with grinding, solution reactive crystallization by cooling, and solution recrystallization by cooling, slurry reactive crystallization was a simple, robust, straightforward, low-constant-temperature, low-solvent-volume, and environmentally benign process giving comparable yield, particle size distribution, and crystallinity. Moreover, the use of a poor solvent in the slurry reactive crystallization enabled the recycling of the mother liquor without any significant loss in yield and crystallinity up to three cycles.

Original languageEnglish
Pages (from-to)2881-2891
Number of pages11
JournalCrystal Growth and Design
Volume19
Issue number5
DOIs
StatePublished - 1 May 2019

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