Optimization of Initial Drug Distribution in Spherical Capsules for Personalized Release

Abstract

Objective: Customization of the rate of drug delivered based on individual patient requirements is of paramount importance in the design of drug delivery devices. Advances in manufacturing may enable multilayer drug delivery devices with different initial drug distributions in each layer.However, a robust mathematical understanding of how to optimize such capabilities is critically needed. The objective of this work is to determine the initial drug loading distribution needed in a spherical drug delivery device such as a capsule in order to obtain a desired drug release profile.Methods: This optimization problem is posed as an inverse mass transfer problem, and optimization is carried out using the solution of the forward problem. Both non-erodible and erodible multilayer spheres are analyzed. Cases with polynomial forms of initial drug distribution are also analyzed. Optimization is also carried out for a case where an initial burst in drug release rate is desired, followed by a constant drug release rate.Results: More than 60% reduction in root-mean-square deviation of the actual drug release rate from the ideal constant drug release rate is reported. Typically, the optimized initial drug distribution in these cases prevents or minimizes large drug release rate at early times, leading to a much more uniform drug release overall. Conclusions:Results demonstrate potential for obtaining a desired drug delivery profile over time by carefully engineering the drug distribution in the drug delivery device. These results may help engineer devices that offer customized drug delivery by combining advanced manufacturing with mathematical optimization.