Design of particle size distribution for custom dissolution profiles by solving the inverse problem

• Published in: Powder technology 2022-01, Vol.395, p.743-757
• Main Authors: Djukaj, Suada, Kolář, Jiří, Lehocký, Róbert, Zadražil, Aleš, Štěpánek, František
• Format: Article
• Language: English
• Subjects: Algorithms; Computer applications; Dissolution; Inverse problem; Inverse problems; Mass balance; Mass-transfer coefficient; Microprocessors; Optimization; Particle size; Particle size distribution; Population balance model; Population balance models; Potassium chloride; Size distribution
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2021.10.023

Dissolution testing is widely used to measure the rate of drug release and predict its in-vivo behavior. The release rate can be controlled by adjusting the particle size distribution (PSD). However, experimental investigation of various particle sizes requires many time-consuming experiments. To reduce the need for them, we propose an optimization framework to solve the inverse problem, i.e., design a PSD that results in a prescribed dissolution profile. The framework's computational core predicts a dissolution profile using a population balance model coupled with a mass balance equation, while the optimization algorithm obtains the inverse solution. The model was validated using mono- and multimodal particle populations of a reference compound (KCl). The validation resulted in a good agreement between the simulated and experimental data. This suggests that the usage of the framework can provide a fast determination of the required PSD, reducing the number of experiments needed. [Display omitted] •Validated approach to analyze both particle size changes and dissolution rate•Population balance model for description of size-dependent dissolution kinetics•Optimization framework can design PSD from a prescribed dissolution profile.