Formulation and Release of Active Pharmaceutical Ingredients Using a Supramolecular Self-Healing Two-Component Gel

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Low-molecular-weight gelators (LMWGs) offer tunable platforms for drug delivery.
• The interaction between active pharmaceutical ingredients (APIs) and gel networks influences drug release kinetics.
• Understanding these interactions is key to designing effective supramolecular drug delivery systems.

Purpose of the Study:

• To investigate the formulation and release characteristics of various APIs within a two-component LMWG system.
• To evaluate the impact of API physicochemical properties (acidity/basicity) on gel formation and drug loading.
• To explore potential ophthalmic applications of these supramolecular gels, particularly for atropine.

Main Methods:

• Formulation of a two-component LMWG from a modified amino acid and aldehyde.
• Differential loading strategies for basic (propranolol, atropine) and acidic (naproxen, rosuvastatin) APIs.
• Drug release studies and characterization using Saturation Transfer Difference (STD) NMR.
• Assessment of gel properties, including thixotropy and erosion, with and without agarose reinforcement.

Main Results:

• Basic APIs could be pre-mixed, while acidic APIs inhibited gelation and required post-assembly diffusion loading.
• Drug release varied significantly; rosuvastatin and propranolol showed low release due to interactions with the gel network, while atropine was rapidly released.
• STD NMR confirmed interactions between aromatic APIs and the gel matrix, influencing release and gel stability. Atropine showed no interaction, leading to rapid release and retention of thixotropic properties.
• Agarose addition reinforced the gel, mitigating erosion during drug release.

Conclusions:

• The choice of API is critical for successful formulation and controlled release from LMWG systems.
• Interactions between APIs and the supramolecular gel network significantly modulate release profiles.
• Atropine, with its favorable release characteristics and lack of interaction with the gel, presents a promising candidate for further development, particularly for ophthalmic applications such as myopia treatment.