Modulating the dehydration conditions of adefovir dipivoxil dihydrate to obtain different physical forms of anhydrate

Kapildev K. Arora, Sunny P. Bhardwaj, Pinal Mistry, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The physical form of anhydrous adefovir dipivoxil (AD), obtained following the dehydration of AD dihydrate, was governed by the kinetics of water removal. The rate and extent of water removal following the dehydration of AD dihydrate was manipulated by altering the sample size, pan configuration, and heating rate in a differential scanning calorimeter. Interestingly, when there was moderate resistance to water removal, a new anhydrous polymorph (melting point 80° C) was obtained. High resistance to water removal resulted in amorphous AD. Variable temperature XRD of AD provided direct and unambiguous evidence of this new polymorph. We have prepared and characterized this new anhydrous polymorph as well as amorphous AD. Based on HPLC, AD dihydrate heated under different conditions in the DSC was observed to be chemically stable. When exposed to water vapor (RH ≥ 80%; 25° C), the new polymorph had a stronger propensity to convert to AD dihydrate than the amorphous anhydrate or AD form I.

Original languageEnglish (US)
Pages (from-to)1056-1064
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume104
Issue number3
DOIs
StatePublished - Mar 2015

Bibliographical note

Funding Information:
This work was partially supported by Ranbaxy Laboratories Limited and the William and Mildred Peters endowment fund. Parts of this work were carried out in the Characterization Facility, University of Minnesota, a member of the NSF-funded Materials Research Facilities Network ( www.mrfn.org ). We are thankful to Dr. Mamta Kapoor and Dr. Karunya Kandimalla for their help with HPLC experiments.

Publisher Copyright:
© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association Keywords: hydrate; polymorph; dehydration; thermal analysis; physical characterization; calorimetry.

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