What is modulating solubility in simulated intestinal fluids?
Eur J Pharm Sci
; 41(3-4): 452-7, 2010 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-20656026
ABSTRACT
The aim of this study was to understand which parameters are responsible for the selective modulation of compounds solubility in simulated intestinal fluids. The solubility of 25 chemically diverse reference compounds was measured in simulated intestinal fluid (FaSSIF-V2) and in aqueous phosphate and maleate buffers. Electrostatic interactions between compounds and the bio-relevant medium components seem to explain the different solubility behavior observed for acids and bases. The solubility of ionized acids is not increased in FaSSIF-V2 probably due to electrostatic repulsions with the media components. Lipophilicity plays an important role but mainly for charged bases with a logP>4 (or logD(6.5)>1.9). When the aqueous solubility is mainly driven by lipophilicity, the FaSSIF-V2 components seem to improve the solubility of basic compounds to a greater extent than for compounds whose solubility is limited by crystal packing. These results suggest that ionization, lipophilicity and crystal packing play important but peculiar roles in controlling solubility in FaSSIF-V2 compared to that in aqueous buffer and this information could be useful to guide medicinal chemists and formulation scientists.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Líquidos Corporais
/
Preparações Farmacêuticas
/
Intestinos
Idioma:
En
Revista:
Eur J Pharm Sci
Ano de publicação:
2010
Tipo de documento:
Article