Formulation and Release of Active Pharmaceutical Ingredients using a Supramolecular Self-healing Two-component Gel

TY - JOUR

T1 - Formulation and Release of Active Pharmaceutical Ingredients using a Supramolecular Self-healing Two-component Gel

AU - El-Qarra, Lamisse

AU - Cosottini, Niccolo

AU - Tangsombun, Chayanan

AU - Smith, David K.

PY - 2024/10/14

Y1 - 2024/10/14

N2 - A two-component low-molecular-weight gelator (LMWG) formed from a modified amino acid and an aldehyde was formulated with active pharmaceutical ingredients (APIs). Basic APIs (propranolol, atropine) can be mixed with the LMWG prior to gel assembly while acidic APIs (naproxen, rosuvastatin) inhibit assembly by disrupting the LMWG imine bond and were loaded by diffusion after gel assembly. For diffusion-loaded gels, the API in the liquid-like phase was rapidly released, with the remainder, interacting with gel fibres, retained in the gel. Rosuvastatin release was particularly low, with STD NMR indicating interactions between the aromatic ring and the self-assembled gel network. Propranolol also interacted with the gel via its aromatic unit, and its release led to gel erosion. Using agarose as a polymer gelator additive reinforced the gel, restricting erosion. In contrast, atropine was readily released over a period of hours – it is primarily in the liquid-like phase with STD NMR indicating no interactions with the gel network. The atropine-loaded gel retained its thixotropic properties. Overall, APIs must be carefully chosen to optimise formulation/release. Of the APIs investigated, atropine has most potential for further development. Atropine has applications in treating myopia, and our results suggest potential ophthalmic applications of supramolecular gels.

AB - A two-component low-molecular-weight gelator (LMWG) formed from a modified amino acid and an aldehyde was formulated with active pharmaceutical ingredients (APIs). Basic APIs (propranolol, atropine) can be mixed with the LMWG prior to gel assembly while acidic APIs (naproxen, rosuvastatin) inhibit assembly by disrupting the LMWG imine bond and were loaded by diffusion after gel assembly. For diffusion-loaded gels, the API in the liquid-like phase was rapidly released, with the remainder, interacting with gel fibres, retained in the gel. Rosuvastatin release was particularly low, with STD NMR indicating interactions between the aromatic ring and the self-assembled gel network. Propranolol also interacted with the gel via its aromatic unit, and its release led to gel erosion. Using agarose as a polymer gelator additive reinforced the gel, restricting erosion. In contrast, atropine was readily released over a period of hours – it is primarily in the liquid-like phase with STD NMR indicating no interactions with the gel network. The atropine-loaded gel retained its thixotropic properties. Overall, APIs must be carefully chosen to optimise formulation/release. Of the APIs investigated, atropine has most potential for further development. Atropine has applications in treating myopia, and our results suggest potential ophthalmic applications of supramolecular gels.

U2 - 10.1002/chem.202402530

DO - 10.1002/chem.202402530

M3 - Article

SN - 0947-6539

JO - Chemistry : A European Journal

JF - Chemistry : A European Journal

M1 - e202402530

ER -