Wilson VR(1), Mugheirbi NA(1), Mosquera-Giraldo LI(1), Deac A(1), Moseson DE(1), Smith DT(1), Novo DC(2), Borca CH(3), Slipchenko LV(4), Edgar KJ(2), Taylor LS(1). Author information:
(1)Department of Industrial & Physical Pharmacy, College of Pharmacy, Purdue
University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United
(2)Department of Chemistry, College of Science, Virginia Tech, 1040 Drillfield
Drive, Blacksburg, Virginia 24061, United States.
(3)Department of Chemical and Biological Engineering, School of Engineering and
Applied Science, Princeton University, 41 Olden Street, Princeton, New Jersey
08544, United States.
(4)Department of Chemistry, College of Science, Purdue University, 560 Oval
Drive, West Lafayette, Indiana 47907, United States.
Amorphous solid dispersions (ASDs), which consist of a drug dispersed in a polymeric matrix, are increasingly being applied to improve the in vivo performance of poorly water-soluble drugs delivered orally. The polymer is a critical component, playing several roles including facilitating drug release from the ASD, as well as delaying crystallization from the supersaturated solution generated upon dissolution. Certain ASD formulations dissolve to produce amorphous drug-rich nanodroplets. The interaction of the polymer with these nanodroplets is poorly understood but is thought to be important for inhibiting crystallization in these systems. In this study, the impact of ionic polymers on the crystallization kinetics of enzalutamide from supersaturated solutions containing different amounts of amorphous nanodroplets was evaluated by determination of nucleation induction times. The amount of the polymer associated with the drug nanodroplets was also determined. When comparing two polymers, hydroxypropylmethyl cellulose acetate succinate (HPMCAS) and Eudragit E PO, it was found that the crystallization tendency and physical properties of the drug nanodroplets varied in the presence of these two polymers. Both polymers distributed between the aqueous phase and the drug-rich nanodroplets. A greater amount of Eudragit E PO was associated with the drug-rich nanodroplets. Despite this, Eudragit E PO was a less-effective crystallization inhibitor than HPMCAS in systems containing nanodroplets. In conclusion, in supersaturated solutions containing amorphous nanodroplets, the extent of association of a polymer with the drug nanodroplet does not solely predict crystallization inhibition.
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