Continuous tank reactor synthesis of highly substituted sulphobutylether β-cyclodextrins

Tammy Savage, John Mitchell, Vivek Trivedi, Stephen Wicks, Laura J. Waters

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Batch synthesis of sulphobutyl ether β-cyclodextrin (also known as SBE-β-CD or SBECD) is a process effectively divided into three main stages, i.e. initial reagent dissolution, a sulphoalkylation reaction and final reaction quenching. This reaction is followed by downstream processing and purification, and ultimate isolation of the solid SBECD material. However, a feature associated with using this synthetic method is that a high proportion of lower substituted SBECD is observed. There is therefore a need to provide an improved synthetic method for producing higher substituted cyclodextrins. The authors here present a Continuous Tank Reactor (CTR) method for preparing sulphobutyl ether-cyclodextrins. The method comprises first contacting cyclodextrin with a base to form activated cyclodextrin. The method then involves separately contacting the activated cyclodextrin with an 1,4-butane sultone to form sulphoalkyl ether-cyclodextrin. The activation reaction is carried out in batch synthesis mode and the sulphoalkylation reaction is carried out under continuous flow conditions resulting in a novel method for the synthesis of highly derivatised cyclodextrins. The work is particularly concerned with producing controlled substitution in sulphobutyl ether β-cyclodextrins and novel compositions of highly substituted sulphoalkyl ether β-cyclodextrins are described.

LanguageEnglish
Pages862-868
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume495
Issue number2
DOIs
Publication statusPublished - 30 Nov 2015

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Cyclodextrins
Ether
beta-Cyclodextrins
SBE4-beta-cyclodextrin

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Savage, Tammy ; Mitchell, John ; Trivedi, Vivek ; Wicks, Stephen ; Waters, Laura J. / Continuous tank reactor synthesis of highly substituted sulphobutylether β-cyclodextrins. In: International Journal of Pharmaceutics. 2015 ; Vol. 495, No. 2. pp. 862-868.
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Continuous tank reactor synthesis of highly substituted sulphobutylether β-cyclodextrins. / Savage, Tammy; Mitchell, John; Trivedi, Vivek; Wicks, Stephen; Waters, Laura J.

In: International Journal of Pharmaceutics, Vol. 495, No. 2, 30.11.2015, p. 862-868.

Research output: Contribution to journalArticle

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T1 - Continuous tank reactor synthesis of highly substituted sulphobutylether β-cyclodextrins

AU - Savage, Tammy

AU - Mitchell, John

AU - Trivedi, Vivek

AU - Wicks, Stephen

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