title: Role of Water Sorption in Tablet Crushing Strength, Disintegration, and Dissolution.
abstract: Drugs formulated as tablets are subjected to accelerated stability conditions with the goal of identifying a stable formulation that will exhibit a sufficiently long shelf life. Water sorption at a condition such as 40°C/75% RH can result in significant changes in tablet properties such as a decrease in dissolution rate, the cause of which may be difficult to interpret, given the complex nature of ingredients and their interactions in a tablet. In this research, three drugs, displaying a wide range of physicochemical properties, were formulated with commonly used diluents, disintegrants, and binders, using a design of experiments approach. The tablets were stored at accelerated conditions and assessed for content, dissolution, disintegration, and crushing strength, as well as other properties. The research demonstrated many water-induced effects in tablet properties. Due to the experimental design approach that revealed many interactions, it was possible to interpret all of the changes observed in tablet crushing strength, disintegration, and dissolution for the drugs using a common set of physical principles. Specifically, the relevant factors considered were (1) mechanical properties of materials, (2) water sorption surface effects in surface diffusion and capillary condensation, (3) water sorption bulk effects for amorphous materials such as viscous flow/spreading, and (4) water-induced stress on interparticle bonding arising from volume expansion. These physical principles enable a comprehensive interpretation of the complex changes observed in tablet properties, which should be valuable in the design of tablet formulations that will be stable to accelerated storage conditions.
authors.affiliation: Zeeh Pharmaceutical Experiment Station, School of Pharmacy, University of Wisconsin - Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA. mark.sacchetti@wisc.edu.|School of Pharmacy, University of Wisconsin - Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA. mark.sacchetti@wisc.edu.
authors.forename: M
authors.initials: M
authors.lastname: Sacchetti
authors.affiliation: School of Pharmacy, University of Wisconsin - Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA.
authors.forename: R
authors.initials: R
authors.lastname: Teerakapibal
authors.affiliation: School of Pharmacy, University of Wisconsin - Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.affiliation: Zeeh Pharmaceutical Experiment Station, School of Pharmacy, University of Wisconsin - Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Elder
mesh_terms: D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D014867:Water / Q000737:chemistry
chemical_list: D013607:Tablets; D014867:Water
keywords: accelerated stability; design of experiments; reduced dissolution rate; tablet crushing strength; water sorption effects in tablets