Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10162384 | Journal of Pharmaceutical Sciences | 2014 | 7 Pages |
Abstract
The antifungal drug, 5-fluorocytosine (FC), is marketed as a capsule (250 or 500Â mg strength) instead of the preferred tablet dosage form. Through systematic characterization of solid-state properties, including mechanical properties, we identify tabletability and poor physical stability of FC as the problems that likely have prevented the successful development of a FC tablet product. We then design an FC oxalate 2:1 salt (FCOXA21), based on established relationship between crystal structure and properties, to address these deficient properties. FCOXA21 is subsequently used to develop a direct compression tablet product using predictive and material-sparing powder characterization tools, that is, ring shear cell for powder flowability and compaction simulator for powder tabletability. The initial tablet formulation, which contains 84.5% (wt %) FCOXA21, exhibits excellent tabletability but inadequate flowability. We solve the powder flowability problem through controlling the particle size of FCOXA21. A batch of FCOXA21 tablets (500Â mg FC equivalent dose) is then prepared. Finally, systematic evaluation on tablet weight variation, content uniformity, friability, and dissolution using standard methods confirms the commercial manufacturability of FC tablets. Through this work, we have demonstrated the potential of integrated crystal and particle engineering in expediting the development of tablet products of challenging drugs using the economical direct compression process. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1126-1132, 2014
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Sathyanarayana Reddy Perumalla, Changquan Calvin Sun,