We examined the potential of the spherical cocrystallization (SCC) technology in simultaneously enhancing tablet manufacturability and dissolution of poorly soluble drugs by developing a mini-tablet formulation of piroxicam. The manufacturing of mini-tablets using a direct compression (DC) process is more challenging than conventional tablets because of the much stricter requirement on the micromeritic properties of formulated powders. The SCC process in this work involved two steps: 1) preparing a new piroxicam-ferulic acid (PRX-FA) cocrystal, and 2) forming spherical agglomerates with the aid of a suitable bridging liquid. The PRX-FA cocrystal exhibited enhanced solubility as well as improved plasticity. The bridging liquid, a mixture of chloroform and ethyl acetate (EA) (1: 2, v/v), was chosen based on the high computed adsorption energy of chloroform and EA on morphologically dominating crystal faces of PRX-FA. The improved flowability, tabletability, and dissolution rate of spherical PRX-FA enabled the successful development of a DC mini-tablet formulation with a high PRX loading (41 wt%). This example shows that SCC is a powerful enabling technology for DC tablet formulation development of challenging drugs.
Bibliographical noteFunding Information:
H.C. was partially supported by a David J.W. Grant & Marilyn J. Grant Fellowship from the Department of Pharmaceutics, University of Minnesota (2019-2020). We thank the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported in this paper. URL: http://www.msi.umn.edu . The Bruker-AXS D8 Venture diffractometer was purchased through a grant from NSF/MRI (#1229400) and the University of Minnesota. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network (NNCI) under Award Number ECCS-1542202.
- Spherical cocrystallization
PubMed: MeSH publication types
- Journal Article