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

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