TY - JOUR
T1 - Amino acid hydrotropes to increase the solubility of indomethacin and carbamazepine in aqueous solution
AU - Alsalhi, Mohammed Suleiman
AU - Chan, K. L. Andrew
N1 - Funding Information:
We would like to extend our thanks to Dr Paul Royall and Professor Stuart Jones, King's college London, London for advice and King Saud university (KSA), Riyadh, Saudi Arabia for scholarship and financial support.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/4/5
Y1 - 2022/4/5
N2 - A number of amino acids (AA) has been investigated as promising hydrotropes to improve the solubility of biopharmaceutics classification system (BCS) class II drugs carbamazepine (CBZ) and indomethacin (IND) via specific complexations in aqueous solution. The aim of this work is to understand the molecular basis of these hydrotropic interactions by investigating the two model drugs combined with 12 amino acids including phenylalanine, tryptophan, isoleucine, proline, valine, glycine, serine, threonine, arginine, lysine, histidine and aspartic acid in water at 25 °C, 30 °C and 45 °C. The amino acids were chosen based on their different side chains (neutral aromatic, aliphatic, polar charged or uncharged) to investigate their hydrotropic performance. A linear solubility curve was observed between indomethacin and mono-neutral hydrophobic amino acids (phenylalanine, tryptophan, isoleucine, proline and valine) well beyond 1:1 molar ratio indicating the interaction is predominantly non-ionic between the drug and the hydrotropes. Interestingly, the aqueous solubility of carbamazepine (a neutral compound) was enhanced by neutral, charged basic or acidic amino acids, confirming the presence of hydrophobic interactions that involve H-bonds, H/π and π/π stacking and the results were confirmed by UV-Vis spectroscopy. A combination of multiple neutral amino acids showed additive hydrotropic effect in indomethacin solubility with up to 7-folds increases. This study demonstrates for the first time the potential of amino acids as hydrotropes to improve aqueous solubility of poorly water-soluble drugs, which is important for pharmaceutical development.
AB - A number of amino acids (AA) has been investigated as promising hydrotropes to improve the solubility of biopharmaceutics classification system (BCS) class II drugs carbamazepine (CBZ) and indomethacin (IND) via specific complexations in aqueous solution. The aim of this work is to understand the molecular basis of these hydrotropic interactions by investigating the two model drugs combined with 12 amino acids including phenylalanine, tryptophan, isoleucine, proline, valine, glycine, serine, threonine, arginine, lysine, histidine and aspartic acid in water at 25 °C, 30 °C and 45 °C. The amino acids were chosen based on their different side chains (neutral aromatic, aliphatic, polar charged or uncharged) to investigate their hydrotropic performance. A linear solubility curve was observed between indomethacin and mono-neutral hydrophobic amino acids (phenylalanine, tryptophan, isoleucine, proline and valine) well beyond 1:1 molar ratio indicating the interaction is predominantly non-ionic between the drug and the hydrotropes. Interestingly, the aqueous solubility of carbamazepine (a neutral compound) was enhanced by neutral, charged basic or acidic amino acids, confirming the presence of hydrophobic interactions that involve H-bonds, H/π and π/π stacking and the results were confirmed by UV-Vis spectroscopy. A combination of multiple neutral amino acids showed additive hydrotropic effect in indomethacin solubility with up to 7-folds increases. This study demonstrates for the first time the potential of amino acids as hydrotropes to improve aqueous solubility of poorly water-soluble drugs, which is important for pharmaceutical development.
UR - http://www.scopus.com/inward/record.url?scp=85126100721&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2022.121591
DO - 10.1016/j.ijpharm.2022.121591
M3 - Article
SN - 0378-5173
VL - 617
JO - INTERNATIONAL JOURNAL OF PHARMACEUTICS
JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS
M1 - 121591
ER -