Solid-state Characteristics of Amorphous Sodium Indomethacin Relative to Its Free Acid

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 1999 Sep 1

PMID 10468018

Citations 18

Authors

P Tong

G Zografi

Affiliations

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Abstract

Purpose: Having previously studied the amorphous properties of indomethacin (IN) as a model compound for drugs rendered amorphous during processing, we report on the formation and characterization of its sodium salt in the amorphous state and a comparison between the two systems.

Methods: Sodium indomethacin (SI) was subjected to lyophilization from aqueous solution, rapid precipitation from methanol solution, and dehydration followed by grinding to produce, in each case, a completely amorphous form. The amorphous form of SI was analyzed using DSC, XRD, thermomicroscopy and FTIR. The method of scanning rate dependence of the glass transition temperature, Tg, was used to estimate the fragility of the SI system. Enthalpy relaxation experiments were carried out to probe the molecular mobility of the SI system below Tg.

Results: The amorphous form of SI formed by different methods had a Tg equal to 121 degrees C at a scanning rate of 20 degrees C/min. This compares with a Tg for indomethacin of 45 degrees C. Estimation of fragility by the scanning rate dependence of Tg indicates no significant differences in fragility between ionized and unionized forms. Enthalpy relaxation measurements reveal very similar relaxation patterns between the two systems at the same degree of supercooling relative to their respective Tg values.

Conclusions: The amorphous form of SI made by various methods has a Tg that is about 75 degrees C greater than that of IN, most likely because of the greater density and hence lower free volume of SI. Yet, the change of molecular mobility as a function of temperature relative to Tg is not very different between the ionized and unionized systems.

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