PhEq_bootstrap is a free software tool that uses the similarity factor (f 2 ) to assess dissolution profile similarity in cases of large data variability. Its theoretical background is founded on bootstrapping, a statistical technique used to simulate the distribution of f 2 values based on the available sample. It allows both justification of profile similarity and prospective simulations for the establishment of the formulation development endpoint. The software is FOSS (free open-source software) and is available online (1).

Low solubility of active pharmaceutical compounds (APIs) remains an important challenge in dosage form development process. In the manuscript, empirical models were developed and analyzed in order to predict dissolution of bicalutamide (BCL) from solid dispersion with various carriers. BCL was chosen as an example of a poor watersoluble API. Two separate datasets were created: one from literature data and another based on in-house experimental data. Computational experiments were conducted using artificial intelligence tools based on machine learning (AI/ML) with a plethora of techniques including artificial neural networks, decision trees, rule-based systems, and evolutionary computations. The latter resulting in classical mathematical equations provided models characterized by the lowest prediction error. In-house data turned out to be more homogeneous, as well as formulations were more extensively characterized than literature-based data. Thus, in-house data resulted in better models than literature-based data set. Among the other covariates, the best model uses for prediction of BCL dissolution profile the transmittance from IR spectrum at 1260 cm −1 wavenumber. Ab initio modeling-based in silico simulations were conducted to reveal potential BCL-excipients interaction. All crucial variables were selected automatically by AI/ML tools and resulted in reasonably simple and yet predictive models suitable for application in Quality by Design (QbD) approaches. Presented data-driven model development using AI/ML could be useful in various problems in the field of pharmaceutical technology, resulting in both predictive and investigational tools revealing new knowledge.

Introduction of a new drug to the market is a challenging and resource-consuming process. Predictive models developed with the use of artificial intelligence could be the solution to the growing need for an efficient tool which brings practical and knowledge benefits, but requires a large amount of high-quality data. The aim of our project was to develop quantitative structure–activity relationship (QSAR) model predicting serotonergic activity toward the 5-HT1A receptor on the basis of a created database. The dataset was obtained using ZINC and ChEMBL databases. It contained 9440 unique compounds, yielding the largest available database of 5-HT1A ligands with specified pKi value to date. Furthermore, the predictive model was developed using automated machine learning (AutoML) methods. According to the 10-fold cross-validation (10-CV) testing procedure, the root-mean-squared error (RMSE) was 0.5437, and the coefficient of determination (R2) was 0.74. Moreover, the Shapley Additive Explanations method (SHAP) was applied to assess a more in-depth understanding of the influence of variables on the model’s predictions. According to to the problem definition, the developed model can efficiently predict the affinity value for new molecules toward the 5-HT1A receptor on the basis of their structure encoded in the form of molecular descriptors. Usage of this model in screening processes can significantly improve the process of discovery of new drugs in the field of mental diseases and anticancer therapy.

Oral medicines represent the largest pharmaceutical market area. To achieve a therapeutic effect, a drug must penetrate the intestinal walls, the main absorption site for orally delivered active pharmaceutical ingredients (APIs). Indeed, predicting drug absorption can facilitate candidate screening and reduce time to market. Algorithms are available with good prediction accuracy that however focus only on solubility. In this work, we focused on drug permeability looking at human intestinal absorption as a marker for intestinal bioavailability. Being of considerable therapeutic relevance, APIs with serotonergic activity were selected as a dataset. Due to process complexity, experimental data scarcity, and variability, we turned toward an artificial intelligence (AI)-based system, which is a hierarchical combination of classification and regression models. This combination of seemingly two models into a single system widens the space of molecules classified as highly permeable with high accuracy. The specialized and optimized system enables in silico and structure-based prediction with a high degree of certainty. Predictions in external validation allowed correct selection of the 38% of highly permeable molecules without any false positives. The proposed system based on AI represents a promising tool useful for oral drug screening at an early stage of drug discovery and development. Datasets and the obtained models are available on the GitHub platform ().

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