| Colloidal phase behavior of pH-responsive, amphiphilic PEGylated poly(carboxylic acid)s and effect on kinetic solubility under acidic conditions. | |
| | |
MedLine Citation:
|
PMID: 19698080 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
PEGylated poly(carboxylic acid)s, PEG-b-PCAs, were evaluated as additives for solubilized oral formulations of weakly acidic compounds. Micelles of poly(ethylene glycol)-block-poly(acrylic acid), PEG-b-PAA, and poly(ethylene glycol)-block-poly(methacrylic acid), PEG-b-PMAA, were prepared. Fluorescence spectroscopy and dynamic light scattering revealed that both polymers assemble into nanoscopic structures (< 200 nm) in acidic media and exhibit pH-sensitive colloidal phase behavior. Using a solvent evaporation technique, the block copolymers and corresponding PCA homopolymers were incorporated into PEG3350-based solid dispersions. The kinetic solubility profile of a BMS compound, BMS-A (Seq ~ 12.5 mug/mL at pH 1.1) in 0.1 N HCl was monitored as a function of polymer composition. While BMS-A precipitated rapidly in 0.1 N HCl in the absence of PEG-b-PCAs, a supersaturated level of ca. 400 mug/mL was maintained for variable lengths of time in the presence of PEG-b-PCAs. Although the kinetic solubility of BMS-A was also enhanced in the presence of the PCA homopolymers, the relative magnitude and duration of supersaturation as a function of polymer composition suggests that micellar solubilization, rather than specific interaction, contributes to enhanced solubility of BMS-A in 0.1 N HCl. Under acidic conditions, pH-responsive PEG-b-PCAs may offer the kinetic supersaturation necessary to minimize precipitation of compounds which have limited solubility in acidic milieu. |
| | |
Authors:
|
Monica L Adams; Venkatramana M Rao; Ajit Thakur; Munir A Hussain |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2009-8-24 |
Journal Detail:
|
Title: Pharmaceutical development and technology Volume: - ISSN: 1097-9867 ISO Abbreviation: Pharm Dev Technol Publication Date: 2009 Aug |
Date Detail:
|
Created Date: 2009-8-24 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9610932 Medline TA: Pharm Dev Technol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Biopharmaceutics Research and Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Potential antifungal effects of human platelets against zygomycetes in vitro.
Next Document: The neurogenic basic helix-loop-helix transcription factor neuroD6 concomitantly increases mitochond...