title: Enabling the Tablet Product Development of 5-Fluorocytosine by Conjugate Acid Base Cocrystals.
abstract: 5-Fluorocytosine (FC) is a high-dose antifungal drug that challenges the development of a tablet product due to poor solid-state stability and tabletability. Using 2 pharmaceutically acceptable conjugate acid base (CAB) cocrystals of FC with HCl and acesulfame, we have developed commercially viable high loading FC tablets. The tablets were prepared by direct compression using nano-coated microcrystalline cellulose Avicel PH105 as a tablet binder, which provided both excellent tabletability and good flowability. Commercial manufacturability of formulations based on both CAB cocrystals was verified on a compaction simulator. The results from an expedited friability study were used to set the compaction force, which yielded tablets with sufficient mechanical strength and rapid tablet disintegration. This work demonstrates the potential value of CAB cocrystals in drug product development.
authors.affiliation: Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Sathyanarayana R
authors.initials: SR
authors.lastname: Perumalla
authors.affiliation: Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Shubhajit
authors.initials: S
authors.lastname: Paul
authors.affiliation: Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455. Electronic address: sunx0053@umn.edu.
authors.forename: Changquan C
authors.initials: CC
authors.lastname: Sun
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization / Q000379:methods; D005437:Flucytosine / Q000138:chemical synthesis*; D006851:Hydrochloric Acid / Q000138:chemical synthesis; D013607:Tablets; D013718:Tensile Strength; D013843:Thiazines / Q000138:chemical synthesis; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000935:Antifungal Agents; D013607:Tablets; D013843:Thiazines; D005437:Flucytosine; C006362:acetosulfame; D006851:Hydrochloric Acid
keywords: cocrystals; crystal engineering; formulation; powder technology; tablet