Untitled

Abstract

Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.

Mechanistic Computational Modeling of Implantable, Bioresorbable Drug Release Systems

“…[ 20 ] Random chain scission has the effect of dramatically reducing the average molecular weight of the polymer, while end chain scission more efficiently produces acidic byproducts. Experimental data has shown that both are necessary in modeling the degradation of polymer, [ 47,52–56 ] therefore we expand Equation to include both end and random chain scission, which is defined by the equations: $$$$\begin{equation}\frac{{d{R}_{es}}}{{dt}} = \left[ {{k}_{e1}{C}_{end} + {k}_{e2}{C}_{end}{C}_{H + }} \right]\ Mask\end{equation}$$$$ $$$$\begin{equation}\frac{{d{R}_{rs}}}{{dt}} = \left[ {{k}_{r1}{C}_e + {k}_{r2}{C}_e{C}_{H + }} \right]\ Mask\end{equation}$$$$ $$$$\begin{equation}\frac{{d{R}_s}}{{dt}} = \frac{{d{R}_{es}}}{{dt}}\ + \frac{{d{R}_{rs}}}{{dt}}\end{equation}$$$$where R es is end chain scission, k e 1 is the non‐catalytic end scission rate constant, C end is the concentration of terminal ester bonds available for end chain scission, k e 2 is the auto‐catalytic end scission rate constant, R rs is random chain scission, k r 1 is the non‐catalytic random scission rate constant, C e is the concentration of interior ester bonds available for random chain scission, and k r 2 is the auto‐catalytic random scission rate constant.…”

“…where R ol is the total concentration of short polymer chains produced over reaction time, C e0 is the initial concentration of interior ester bonds and l is the length in ester bonds of the oligomer chain. [ 56,58 ] In this work we continue by applying equation to evaluate the production of oligomers, while Pan et al. continues by generalizing Equation to allow for empirical tuning.…”

“…[20] Random chain scission has the effect of dramatically reducing the average molecular weight of the polymer, while end chain scission more efficiently produces acidic byproducts. Experimental data has shown that both are necessary in modeling the degradation of polymer, [47,[52][53][54][55][56] therefore we expand Equation 4 to include both end and random chain scission, which is defined by the equations: . G) COMSOL simulation for drug diffusion out of 50 μm microsphere with a 2D slice geometry and heterogeneous initial drug distribution derived from confocal images, 6 hours after formation.…”

“…where R ol is the total concentration of short polymer chains produced over reaction time, C e0 is the initial concentration of interior ester bonds and l is the length in ester bonds of the oligomer chain. [56,58] In this work we continue by applying equation 9f to evaluate the production of oligomers, while Pan et al continues by generalizing Equation 9f to allow for empirical tuning. [59] The distinguishing characteristic between C ol and R ol is that C ol is reduced when the oligomers diffuse out of the polymer matrix, while R ol accounts for all the ester bonds of oligomers that have been produced.…”

“…through dissolved polymer. [56] For the ISFI, significant swelling was observed, and to account for the increased diffusivity of each of components through the polymer during the swelling of the implant we modified Equation 22 to include for free-volume theory. The relationship between component diffusivity through the polymer and the implant volume expansion is based on the generalized free-volume theory proposed by Fujita et al [60][61][62] based on work by Turnbull and Cohen, [63] and further developed Peppas et al [64][65][66][67][68][69][70] .…”