In silico formulation optimization and particle engineering of pharmaceutical products using a generative artificial intelligence structure synthesis method

Pharmaceutical drug dosage forms are critical for ensuring the effective and safe delivery of active pharmaceutical ingredients to patients. However, traditional formulation development often relies on extensive lab and animal experimentation, which can be time-consuming and costly. This manuscript presents a generative artificial intelligence method that creates digital versions of drug products from images of exemplar products. This approach employs an image generator guided by critical quality attributes, such as particle size and drug loading, to create realistic digital product variations that can be analyzed and optimized digitally. This paper shows how this method was validated through two case studies: one for the determination of the amount of material that will create a percolating network in an oral tablet product and another for the optimization of drug distribution in a long-acting HIV inhibitor implant. The results demonstrate that the generative AI method accurately predicts a percolation threshold of 4.2% weight of microcrystalline cellulose and generates implant formulations with controlled drug loading and particle size distributions. Comparisons with real samples reveal that the synthesized structures exhibit comparable particle size distributions and transport properties in release media.