Rapidly dissolving repaglinide powders produced by the ultra-rapid freezing process
AUTOR(ES)
Purvis, Troy
FONTE
Springer-Verlag
RESUMO
The objective of the study was to produce rapidly dissolving formulations of the poorly water-soluble drug repaglinide using an innovative new technology, ultra-rapid freezing (URF), and to investigate the influence of excipient type on repaglinide stability. Repaglinide compositions containing different types and levels of excipients and different drug potencies (50%–86%) were produced by the URF technology. Repaglinide/excipient solutions were frozen on a cryogenic substrate, collected, and lyophilized to form a dry powder. Surfactants, including sodium dodecyl sulfate, and alkalizing agents such as diethanolamine (DEA) and tromethamine (TRIS) were incorporated into the compositions. Forced degradation of repaglinide was conducted under stressed conditions (eg, elevated temperature, exposure to peroxide) to determine the stability of the drug in such environments. The solubility of repaglinide increased as a function of increasing pH; therefore, incorporation of an alkalizing agent into the URF formulations increased the drug's solubility. Drug instability resulted when the drug was exposed to pH values above 9.0. URF formulations containing alkalizing agents showed no degradation or spontaneous recrystallization in the formulation, indicating that increased stability was afforded by processing. URF processing created nanostructured drug/excipient particles with higher dissolution rates than were achieved for unprocessed drug. Alkalizing agents such as TRIS and DEA, present at levels of 25% to 33% wt/wt in the formulations, did not cause degradation of the drug when processed using URF. URF processing, therefore, yielded fast-dissolving formulations that were physically and chemically stable, resistant to alkali degradation or spontaneous recrystallization in the formulation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2750554Documentos Relacionados
- ULTRA-RAPID FREEZING OF BOVINE EMBRYOS WITH ETHYLENE GLYCOL WITH OR WITHOUT TREHALOSE.
- SURVIVAL OF MICROORGANISMS AFTER ULTRARAPID FREEZING AND THAWING
- Pharmacogenetics: the slow, the rapid, and the ultrarapid.
- Mycobacteriocins produced by rapidly growing mycobacteria are Tween-hydrolyzing esterases.
- Low temperature synthesis of magnesium oxide and spinel powders by a sol-gel process