# PILL-CoDe: Inverse Design of Polypills via Automatic Differentiation for Prescribed Drug-Release Kinetics

Source: [PILL-CoDe: Inverse Design of Polypills via Automatic Differentiation for Prescribed Drug-Release Kinetics](<https://www.sota2.com/research/paper/693a50206cfd488761a54b53>)

Collection index: [llms.txt](<https://www.sota2.com/research/llms.txt>)

Data updated: 2026-07-18T05:00:05.624Z

Authors: Rahul Kumar Padhy, Aaditya Chandrasekhar, Amir M. Mirzendehdel

Published: 2025-12-09T22:08:50.000Z

## Abstract

Polypills are single oral dosage forms that combine multiple active pharmaceutical ingredients and excipients, enabling fixed-dose combination therapies, coordinated multi-phase release, and precise customization of patient-specific treatment protocols. Recent advances in additive manufacturing facilitate the physical realization of multi-material excipients, offering superior customization of target release profiles. However, polypill formulations remain tuned by ad hoc parameter sweeps. The current design workflows are ill-suited for the systematic exploration of the high-dimensional space of shapes, compositions, and release behaviors. We present PILL-CoDe, a polypill co-design framework that simultaneously optimizes tablet geometry and excipient distribution to match prescribed drug-release kinetics. The framework couples a supershape parametrization of the pill geometry with a coordinate-based neural network representation of the excipient distribution, and governs dissolution through a coupled system of modified Allen-Cahn and Fickian diffusion equations. Implemented in JAX, the entire pipeline is end-to-end differentiable, with automatic differentiation providing exact sensitivities for gradient-based co-optimization of shape and composition under manufacturability constraints. We demonstrate the method through single-phase and multi-excipient case studies, showing accurate matching of both monotonic and non-monotonic target release profiles.

## Recorded benchmark results

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## Original sources and implementation

[Original paper](<https://arxiv.org/abs/2512.09154>)

[PDF](<https://arxiv.org/pdf/2512.09154.pdf>)