Abstract:
:Amorphous solids and crystalline salts are both of interest as a means of improving the dissolution characteristics and apparent solubility of poorly water soluble active pharmaceutical ingredients which have low bioavailability in humans. The theory and selection of both crystalline drug substance salt forms and amorphous products have been extensively studied. However, less is known about the impact of different counterions on the properties of amorphous drug substance salts. In this study, several salts of either nicardipine or propranolol were prepared and characterized with respect to glass transition temperature, crystallization tendency and moisture sorption behavior. Although the moisture sorption behavior and crystallization tendency varied depending on the counterion used, no trends were readily apparent. The glass transition temperature was found to be dependent on the counterion used to form the salt, and was higher in all instances for the salts than for the neutral compound. Several molecular descriptors were calculated for the various counterions, and multivariate analysis was used to build a model that successfully correlated Tg with a number of these parameters. Important parameters which influenced Tg included counterion pKa and electrophilicity index. In conclusion, it is apparent that, as for crystalline salts, the counterion has an effect on the properties of amorphous materials.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Towler CS,Li T,Wikström H,Remick DM,Sanchez-Felix MV,Taylor LSdoi
10.1021/mp8000342subject
Has Abstractpub_date
2008-11-01 00:00:00pages
946-55issue
6eissn
1543-8384issn
1543-8392journal_volume
5pub_type
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