Controlled release of pharmaceutical agents using eutectic modified gelatin

Abstract

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

Bioadhesive eutectogels supporting drug nanocrystals for long-acting delivery to mucosal tissues

“…These include a limited area, secretion of fluids, enzymatic degradation, poor tissue penetration, and palatability in the case of oral products [ 17 ]. However, scarce studies on eutectogels as drug delivery systems have been conducted so far, and to the best of our knowledge, NCs formulations have not been considered in the formulation design [ 18 ]. Poly(2-hydroxyethyl methacrylate) eutectogels hosting choline chloride (ChCl)/ascorbic acid (2:1) or ChCl/fructose (2:1) DES have been recently developed for oral delivery of sunitinib malate or indomethacin, respectively [ 19 , 20 ].…”

Selective Extraction of Antioxidants by Formation of a Deep Eutectic Mixture through Mechanical Mixing

“…In this study, only two QASs are tested, as not many are currently acceptable for use in cosmetic applications. QAS are generally considered as irritants because they are hygroscopic; however, it is known that DESs containing QAS are significantly less hygroscopic than the pure QAS tested alone . Hence, skin testing is required before they can be used routinely on skin.…”

“…QAS are generally considered as irritants because they are hygroscopic; however, it is known that DESs containing QAS are significantly less hygroscopic than the pure QAS tested alone. 30 Hence, skin testing is required before they can be used routinely on skin. Absorption of water by a ChCl:glycerol (1:2) mixture was shown to be significantly less than that of the pure components tested separately, thus suggesting that QAS involved in a DES should be less irritating than expected.…”

Effect of Graphene Oxide and Temperature on Electrochemical Polymerization of Pyrrole and Its Stability Performance in a Novel Eutectic Solvent (Choline Chloride–Phenol) for Supercapacitor Applications

“… 20 Typically, these are mixtures of quaternary ammonium salts mixed with metal salts or hydrogen bond donors (HBDs), 21 , 22 although others such as the combination of metal salts with HBDs also exist. 23 DESs have been applied in many areas including electrodeposition of metals and alloys, 24 , 25 conducting polymers, 26 , 27 metal finishing, desulfurization, 28 pharmaceuticals, 29 , 30 and energy storage. 31 This is due to the fact that they are cheap, are easy to prepare, are non-volatile, are biodegradable, are insensitive to water, and typically have low toxicity, all of which make their use in large-scale applications highly favorable.…”

“…Typically, these are mixtures of quaternary ammonium salts mixed with metal salts or hydrogen bond donors (HBDs), , although others such as the combination of metal salts with HBDs also exist . DESs have been applied in many areas including electrodeposition of metals and alloys, , conducting polymers, , metal finishing, desulfurization, pharmaceuticals, , and energy storage . This is due to the fact that they are cheap, are easy to prepare, are non-volatile, are biodegradable, are insensitive to water, and typically have low toxicity, all of which make their use in large-scale applications highly favorable. , Several researchers have synthesized various conducting polymers in DESs and studied different associated parameters, including the growth mechanism and cycling stability of polymers in DESs as well as ion and solvent transport. − Indeed, the type of solvent and, thus, the size of the dopant counteranions have a significant effect on all the films’ properties including structure, morphology, and cycling stability, , where the positive charges are produced in the backbone of polymer during oxidation.…”