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  1. Zolkiflee NF, Affandi MMRMM, Majeed ABA
    Eur J Pharm Sci, 2020 Jan 01;141:105111.
    PMID: 31629916 DOI: 10.1016/j.ejps.2019.105111
    Lovastatin (LVS) is an effective therapeutic and prophylactic agent in several cardiovascular disorders. However, it has low bioavailability. This study investigated solute-solvent and solute-cosolute interactions and assessed thermodynamic parameters that contributed to LVS solubility enhancement in the presence of arginine (ARG) as a hydrotropic agent. The electrolytic conductance of LVS-ARG binary system was measured at temperatures from 298.15 K to 313.15 K. Conductometric parameters such as limiting molar conductance was evaluated. Additionally, thermodynamic parameters (ΔG0, ΔH0, ΔS0 and ES) involved in the association process of the solute in the aqueous solution of ARG solution were determined systematically. Solubility markedly improved 43-fold in the LVS-ARG complex compared to LVS alone. The analysed data from values of molar conductance and activation energy suggested favourable solubilisation, with a stronger solute-solvent interaction between LVS-ARG in water at higher temperatures. ARG and LVS complexation caused by strong molecular interactions was confirmed by spectral results. Hence, the addition of ARG as a co-solute was proven to enhance LVS solubility in water. The obtained data will ultimately enable the development of desired highly soluble, more efficient and safer LVS preparations.
  2. Zolkiflee NF, Meor Mohd Affandi MMR, Abdul Majeed AB
    Heliyon, 2023 Apr;9(4):e14363.
    PMID: 37009243 DOI: 10.1016/j.heliyon.2023.e14363
    Levocetirizine dihydrochloride (LCTZ) is a second-generation antihistamine known for its efficacy without sedation. However, the binding mechanism with plasma protein which makes it devoid of sedative effects is yet to be uncovered. In this study, we elucidated thermodynamic parameters of solute-solvent and solute-cosolute interactions between LCTZ, and the amino acids l-alanine (Ala) and l-glutamine (Gln) in aqueous solutions. The volumetric and conductance parameters were calculated using the experimental density and conductance data of aqueous solutions of Ala and Gln (concentration range of 0.02-0.20 mol kg-1) and LCTZ (concentration range of 0.01, 0.07, and 0.13 mol kg-1) at 298.15, 303.15, 308.15, and 313.15 K. Volumetric analysis study revealed that the apparent molar volume (Vφ), limiting apparent molar volume (Vφ 0), and Masson's coefficient (Sv) values indicated predominantly solute-solvent interactions that were influenced by the solute's concentration and temperature. Meanwhile, partial molar expansibilities (Eφ 0), transfer volume ΔtrVφ 0 and Hepler's constant (δ2V0/δT2) established the solution system's structure-breaking tendency. The Gibb's free energy (ΔG0) values derived from conductometry data indicated the system's spontaneity. These calculated constants provided a detailed understanding of the different types of intermolecular interactions found in the ternary (LCTZ + water + amino acids) system.
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