Tailoring aqueous solubility of a highly soluble compound viacocrystallization: effect of coformer ionization, pH sub(max) and solute-solvent interactions

Cocrystals of a nonionizable, water soluble compound (gababentin lactam (GBPL)) with less soluble coformers, are shown to be 2 to 17 times less soluble than GBPL. Cocrystals of GBPL with gentisic acid, 4-hydroxybenzoic acid, 4-aminobenzoic acid and fumaric acid are characterized by carboxylic acid--...

Full description

Saved in:
Bibliographic Details
Published inCrystEngComm Vol. 14; no. 14; pp. 4801 - 4811
Main Authors Maheshwari, Chinmay, Andre, Vania, Reddy, Sreenivas, Roy, Lilly, Duarte, Teresa, Rodriguez-Hornedo, Nair
Format Journal Article
LanguageEnglish
Published 01.06.2012
Subjects
Drug delivery systems
Fumaric acid
Hydrogen bonds
Ionization
Lattices
Solubility
Solubilization
Solvation
Online AccessGet full text

Cover

More Information
Summary:Cocrystals of a nonionizable, water soluble compound (gababentin lactam (GBPL)) with less soluble coformers, are shown to be 2 to 17 times less soluble than GBPL. Cocrystals of GBPL with gentisic acid, 4-hydroxybenzoic acid, 4-aminobenzoic acid and fumaric acid are characterized by carboxylic acid---amide hydrogen bonds between coformer and GBPL, consistent with a previously reported structure of a benzoic acid cocrystal. The lattice and solvation contributions to cocrystal aqueous solubility were evaluated and solvation was found to be the main contribution to solubilization. Cocrystals exhibited pH-dependent solubility and pH sub(max), both of which are described by coformer pK sub(a) and cocrystal K sub(sp) values. These findings have important implications for the characterization and selection of cocrystals for desired drug delivery behavior.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
content type line 23
ObjectType-Feature-1
ISSN:1466-8033
DOI:10.1039/c2ce06615g