TitleSalt solid dispersions
NameGhosh, Anasuya A. (author), Minko, Tamara (chair), Michniak-Kohn, Bozena B (internal member), You, Guofeng (internal member), Zannou, Erika (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionImproving oral bioavailability of poorly water-soluble drugs remains one of the most challenging aspects of drug development. Pharmaceutical salt formation is a widely accepted approach to improve dissolution rate of poorly water-soluble ionic drugs. Nevertheless, the salt formation process is often empirical and may not always lead to desired end product profile. Alternatively, pH-modifiers have been used as formulation components for such compounds. The purpose of this study is to explore the synergies between pH modulating ability offered by a salt form and the dissolution enhancement offered by an amorphous solid dispersion. The hypothesis of this study is that for a weakly basic drug, its solid dispersion with a hydrophilic polymer and a salt-forming acidic counterion should provide dissolution enhancement similar to that of a solid dispersion of its salt. Secondly, for a weakly basic drug if a salt form with a selected counterion cannot be synthesized, then solid dispersion of the drug, the non-salt forming counterion and a hydrophilic polymer could also provide adequate dissolution enhancement. In the present investigation the dissolution enhancement of Cinnarizine, a weakly basic drug, is studied from its solid dispersions containing acidic counterions (organic acids) that have varying ability to form cinnarizine salts. The effect of adding ionic polymers as pH-modifiers is also investigated. Solid dispersions were prepared using melt extrusion technology. Molecular interactions between relevant functional groups of drug and pH-modifiers and the possibility of in situ salt formation during the melt extrusion process were explored. The results of this study systematically offer the benefits of adding acidic counterions during melt extrusion, should a classical salt formation technique fail. A predictive computational model was used to estimate human in vivo plasma profiles by using in vitro dissolution of the developed solid dispersions and the marketed product.
NoteIncludes bibliographical references
Noteby Anasuya A. Ghosh
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.