An investigation into the influence of counterion on the properties of some amorphous organic salts.
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.
Towler
Christopher S
CS
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, USA.
Li
Tonglei
T
Wikström
Håkan
H
Remick
David M
DM
Sanchez-Felix
Manuel V
MV
Taylor
Lynne S
LS
D000327:Adsorption; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D005898:Glass / Q000737:chemistry; D006801:Humans; D006813:Humidity; D015394:Molecular Structure; D015999:Multivariate Analysis; D009529:Nicardipine / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry*; D012492:Salts / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D044366:Transition Temperature; D014867:Water / Q000737:chemistry
D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D012492:Salts; D014867:Water; D011433:Propranolol; D009529:Nicardipine