Merged in silico-in vitro validations of atenolol and amlodipine besylate with excipient interactions for the design of solid oral dosage forms

Abstract

Early understanding and estimation of interactions between the drug and excipients is a crucial step in the preformulation studies. In silico studies, utilising computational methods, were followed by in vitro studies and validation by analytical techniques to identify stable excipients for the development of solid oral dosage forms. In silico studies were conducted using the FormulationDE machine learning tool, which utilises artificial intelligence for data integration. It was found that ATN was compatible, while AMB was incompatible with the selected excipients in in silico studies. In vitro studies, including isothermal stress testing methods and stability profiles of drugs to assess the potential for drug-excipient interactions or compatibility under long-term storage conditions and physiological conditions. These studies were demonstrated, and samples were analysed using high-performance liquid chromatography to quantify the percentage drug degradation with time. In vitro results showed that ATN and AMB were compatible with SmartEx, whereas both drugs were found to be incompatible with Ludipress. FTIR and DSC provide evidence of possible interactions between the selected drug and excipients through spectral band shifts and thermal transitions, respectively. Stability studies of drugs were conducted under gastric pH (1.2) and incubated at 37 °C for four hours to evaluate the resilience of the drugs under physiological conditions and to mimic the gastric environment. The results showed instability of AMB and stability of ATN under the same gastric physiological conditions. This article highlights the importance of integrating in silico with in vitro experimental techniques in preformulation to minimise risk during later stages of formulation development. The results of various studies have directed the future development of ATN-based solid oral dosage forms using thermoplastic SmartEx QD 100 excipients.