Abstract：
:The solubility of a drug is ultimately governed by its chemical potential as it is present in the undissolved solute. For a pharmaceutical amorphous solid dispersion (ASD), its solubility depends on the state and composition of the undissolved solute when the ASD is equilibrated with water. Concerning the undissolved solute phase that can contain up to 3 components (drug, polymer, and water), we developed a complete thermodynamic model to calculate the chemical potential of a drug in the multicomponent, amorphous system. This approach enables the estimation of the true solubility advantage of ASD from calorimetric measurements and moisture sorption isotherms. Both theoretical estimation and experimental studies, using indomethacin (IMC)/Eudragit E ASD systems, show that the solubility advantage of the amorphous IMC is significantly reduced through ASD formation and water partitioning. For the ASD with 70% drug loading, the solubility of IMC is lower than its crystalline counterpart. Our results show that stabilization through the ASD formation and water sorption can be manifested by the lowering of drug solubility; they demonstrate that the core property in ASD development is the drug chemical potential, which is essentially the thermodynamic driving force and can be quantitated using the model presented in this work.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Huang S,Mao C,Williams RO 3rd,Yang CYdoi
10.1016/j.xphs.2016.08.017subject
Has Abstractpub_date
2016-12-01 00:00:00pages
3549-3561issue
12eissn
0022-3549issn
1520-6017pii
S0022-3549(16)41680-1journal_volume
105pub_type
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