Controlled release of pharmaceutical agents using eutectic modified gelatin

Deep eutectic solvent (DES) is a class of ionic liquids, consisting of a mixture generally formed by combining hydrogen bond donors (HBDs) such as alcohols, amides and carboxylic acids with various quaternary ammonium salts. The decrease in melting points of the constituents is due to the charge delocalization during formation of hydrogen bonding between the hydrogen bond acceptor with the hydrogen bond donor. This can be considered one of the main reasons for increasing solubility and absorption of DESs. Most active pharmaceutical ingredients (APIs) have polar functional groups containing amide, carboxylic acid, alcohol or quaternary ammonium groups. These tend to increase the melting point of the compounds, but they can be used to form eutectic mixtures. While this concept has previously used, the combination of quaternary ammonium salts with amides, carboxylic acids and alcohols can result in large depressions of freezing points and so-called deep eutectic solvents are formed. DESs mix readily with water and so could increase the uptake of APIs. In this study, pharmaceutical deep eutectic solvents (PDESs) are formulated from 3 APIs: imipramine HCl, ascorbic acid and catechol. These PDESs were used to plasticise gelatine. It is shown that the materials formed can be used to increase the rate of API uptake via both oral and transdermal delivery modes. Thus, the concentration of the PDESs in solution reaches the maximum before the pure drugs. Particularly for catechol, after 1 s, the dissolution of the PDESs was more than twice that of the pure drug. Moreover, the transdermal delivery mode uptake of the PDES based on imipramine HCl from the patch after 15 min was found to be 65% compared with just imipramine HCl which released only 20%. Graphical abstract