Manufacture and Performance Evaluation of a Stable Amorphous Complex of an Acidic Drug Molecule and Neusilin
In this paper, we explore the use of Neusilin, an inorganic magnesium aluminometasilicate, to stabilize the amorphous form of an acidic drug Sulindac. Both cryomilling and ball milling of the drug with Neusilin were found to produce the amorphous phase. However, the ball‐milled (BM) material exhibit...
Saved in:
Published in | Journal of pharmaceutical sciences Vol. 100; no. 8; pp. 3332 - 3344 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Elsevier Inc
01.08.2011
Wiley Subscription Services, Inc., A Wiley Company Wiley American Pharmaceutical Association Elsevier Limited |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | In this paper, we explore the use of Neusilin, an inorganic magnesium aluminometasilicate, to stabilize the amorphous form of an acidic drug Sulindac. Both cryomilling and ball milling of the drug with Neusilin were found to produce the amorphous phase. However, the ball‐milled (BM) material exhibited superior physical stability when compared with the cryomilled material at 40°C/75% relative humidity. 13C solid‐state nuclear magnetic resonance investigation of the BM material revealed an acid–base reaction between Sulindac and Neusilin. Optimal milling conditions and the kinetics of salt formation were also established. As benchtop milling is a laboratory‐scale process, a scalable process was developed to make Sulindac–Neusilin amorphous drug complex using hot‐melt extrusion (HME). The dissolution properties of the resulting HME material was found to have been improved over the material made by benchtop milling while maintaining similar physical stability. The HME material was used to make tablets using a direct compression method. The HME tablets were found to have better dissolution properties than tablets made from crystalline Sulindac. For the broad class of acidic drugs containing the carboxyl moiety, inorganic silicates such as Neusilin would offer a better choice than organic polymers to stabilize the amorphous phase. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3332–3344, 2011 |
---|---|
Bibliography: | istex:080E7F8CEA65F0BC834B756B15089E75E6A735A9 ark:/67375/WNG-2Q8XFJ18-G ArticleID:JPS22583 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3549 1520-6017 |
DOI: | 10.1002/jps.22583 |