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Combining ibuprofen sodium with cellulosic polymers: a deep dive into mechanisms of prolonged supersaturation.

Abstract：

:The combination of a highly soluble salt form of a drug with a polymeric precipitation inhibitor has the potential to prolong drug supersaturation even following salt disproportionation. In this study, dissolution profiles of ibuprofen sodium in the presence of various cellulosic polymers, including hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), and hydroxypropyl cellulose (HPC), were examined in order to assess degree and duration of supersaturation. In addition, the roles that the polymers played in altering drug solubility, media viscosity, physical form, and particle morphology were also assessed. A deep dive into the mechanisms of supersaturation revealed that intermolecular hydrogen bonding between ibuprofen and HPMC was driving supersaturation through nucleation inhibition and crystal growth modification. Polymer viscosity was proposed as the primary factor prolonging supersaturation of ibuprofen in the presence of MC, while mechanisms other than hydrogen bonding were likely to be attributed to supersaturation with the most hydrophobic polymer evaluated, HPC. Overall, the study suggested that induction of intermolecular interactions between ibuprofen and HPMC were more effective at inhibiting nucleation and maintaining prolonged supersaturation than physical modulation of solution properties, such as viscosity.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Terebetski JL,Michniak-Kohn B

doi

10.1016/j.ijpharm.2014.09.015

subject

Has Abstract

pub_date

2014-11-20 00:00:00

pages

536-46

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(14)00666-8

journal_volume

475

pub_type

杂志文章

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