Abstract
Photocrosslinkable polyanhydrides that undergo surface erosion are suitable materials for controlled-release drug delivery systems. Investigating the impact of different parameters on their erosion behavior is essential before use in drug delivery systems. Although their synthesis is well-established, parameters that may substantially affect the erosion of thiol-ene polyanhydrides including temperature and pH of the media, the geometry of the polymers, and the media shaking rate (the convective force for the polymer erosion), have not yet been studied. This study explores the effects of different environmental and geometric parameters on mass loss (erosion) profiles of polyanhydrides synthesized by thiol-ene photopolymerization. A comparative study on several release kinetic models fitting is also described for a better understanding of the polymer erosion behavior. The results demonstrated that although the temperature was the only parameter that affected the induction period substantially, the mass-loss rate was influenced by the polymer composition, tablet geometry, temperature, pH, and mass transfer (shaking) rate. With regard to geometrical parameters, polymers with the same surface area to volume ratios showed similar mass loss trends despite their various volumes and surface areas. The mass loss of polyanhydride tablets with more complicated geometries than a simple slab was shown to be non-linear, and the kinetic model study indicated the dominant surface erosion mechanism. The results of this study allow for designing and manufacturing efficient delivery systems with a high-predictable drug release required in precision medicine using surface-erodible polyanhydrides.
Highlights
Erosion is the mechanism governing a broad range of chemically mediated controlled-release systems (CRSs) and can occur in the form of bulk and/or surface erosion
We showed the effect of several factors on the mass loss behavior of photocrosslinked
Changing the polymer compositions did not affect the induction period, an increased initial mole ratio of EGDT to polymers with two different compositions (PETMP) resulted in a shorter total erosion time
Summary
Erosion is the mechanism governing a broad range of chemically mediated controlled-release systems (CRSs) and can occur in the form of bulk and/or surface erosion. The highly reproducible and predictable release kinetics of surface-erodible polymers make them desirable for fabricating controlled drug delivery systems (DDSs) [4]. PAHs prepared by melt-condensation showed a linear mass loss profile in a slab geometry resulting in a near zero-order drug release [3,5]. Wafer (a polyanhydride-based implant for locally delivering cancer drug to brain tumors) [10] One reason for their limited clinical use compared to other biodegradable polymers such as polyesters is due to the difficulties in synthesizing them [9]. Advances made in synthesizing PAHs are not matched with a comprehensive erosion study as there are several parameters that can substantially affect the erosion of thiol-ene PAHs. For instance, if the controlled-release drug tablet is formulated for oral delivery, the appropriate geometry is a cylinder or a sphere, not a cuboid. Based on the best-fitted models, cylindrical and cuboid tablets obeyed the Hixson-Crowell and Hopfenberg models, which describe polymers with erosion mechanisms rather than diffusion-controlled systems
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