Exploring the Solubility Behavior of Nifedipine: Insights from Multiple Techniques

Nifedipine, a calcium channel blocker, is effective in managing cardiovascular conditions. However, its variable solubility in different solvent systems poses formulation challenges. Understanding its solubility behavior is crucial for optimizing drug delivery strategies and enhancing therapeutic outcomes. This study employs various techniques rooted in established solubility theories to explore nifedipine solubility across different solvents. Experimental techniques, complemented by computational modelling, including extended Hildebrand solubility approach, Hansen’s approach, and polynomial regression analysis are used. Experimental data on nifedipine solubility in various solvent blends are collected and analyzed to elucidate the underlying molecular interactions driving solubility. The study reveals that nifedipine exhibits complex solubility behavior influenced by factors such as solvent polarity (\({{\delta }_{{2p~~}}} = 3.90{\text{ H}}\)), dispersion forces (\({{\delta }_{{2d}}} = 8.23{\text{ H}}\)), and hydrogen bonding interactions (\({{\delta }_{{2a}}} = 6.65{\text{ H}},{{\;}}{{\delta }_{{2b}}} = 0.93{\text{ H}}),\) as found from four parameter approach. These results align with the chemical structure of nifedipine, offering insight into the drug ability to interact. Hydrogen bonding partial parameters provided a rational explanation for the solubility behavior of nifedipine, highlighting its role as a proton donor and Lewis acid. The technique of ideal solubility intersecting observed mole fraction solubility (10.62 H) proved valuable in predicting nifedipine solubility, particularly when closely aligned with peak solubility (10.13 H). By examining the total solubility parameter values obtained from different methods, it can be concluded that the best solvents for nifedipine fall within \({{\delta }_{1}}\) values ranging from 10 to 13 H. These findings contribute to the understanding of nifedipine solubility and provide insights into the design of effective drug delivery systems.