PharmDE: A new expert system for drug-excipient compatibility evaluation.

Abstract Drug-excipient compatibility study is the essential basis for excipient selection at the pre-formulation stage. According to the pharmaceutical Quality by Design (QbD) principles, a comprehensive understanding of the ingredients' physicochemical properties and a theoretical evaluation of the interaction risk between the drugs and excipients are required for conducting rational compatibility experimental design. Currently, there is an urgent need to establish an artificial intelligence system for researchers to easily get through the problem because it is very inconvenient and hard to utilize those drug-excipient incompatibility data scattered in scientific literature. Here, we designed a knowledge-driven expert system named PharmDE for drug-excipient incompatibility risk evaluation. PharmDE firstly developed an information-rich database to store incompatibility data, covering 532 data items from 228 selected articles. Then, 60 drug-excipient interaction rules were created based on our knowledge and formulation research experiences. Finally, the expert system was developed by organically integrating the database searching and rule-based incompatibility risk prediction, which resulted in four main functionalities: basic search of incompatibility database, data matching by similarity search, drug incompatibility risk evaluation, and formulation incompatibility risk evaluation. PharmDE is expected to be a useful tool for drug-excipient compatibility study and accelerate drug formulation design. It is now freely available at https://pharmde.computpharm.org .