Correlation of Solubility Thermodynamics of Glibenclamide with Recrystallization and In Vitro Release Profile |
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| Authors: | Ravi Maharjan Junoh Jeong Ripesh Bhujel Min-Soo Kim Hyo-Kyung Han Nam Ah Kim Seong Hoon Jeong |
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| Institution: | 1.BK21 FOUR Team, Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Gyeonggi 10326, Korea; (R.M.); (J.J.); (R.B.); (H.-K.H.); (N.A.K.);2.College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 46241, Korea; |
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| Abstract: | The solubility of glibenclamide was evaluated in DMSO, NMP, 1,4-dioxane, PEG 400, Transcutol® HP, water, and aqueous mixtures (T = 293.15~323.15 K). It was then recrystallized to solvate and compressed into tablets, of which 30-day stability and dissolution was studied. It had a higher solubility in 1,4-dioxane, DMSO, NMP (Xexp = 2.30 × 103, 3.08 × 104, 2.90 × 104) at 323.15 K, its mixture (Xexp = 1.93 × 103, 1.89 × 104, 1.58 × 104) at 298.15 K, and 1,4-dioxane (w) + water (1−w) mixture ratio of w = 0.8 (Xexp = 3.74 × 103) at 323.15 K. Modified Apelblat (RMSD ≤ 0.519) and CNIBS/R-K model (RMSD ≤ 0.358) suggested good comparability with the experimental solubility. The minimum value of ΔG° vs ΔH° at 0.70 < x2 < 0.80 suggested higher solubility at that molar concentration. Based on the solubility, it was recrystallized into the solvate, which was granulated and compressed into tablets. Among the studied solvates, the tablets of glibenclamide dioxane solvate had a higher initial (95.51%) and 30-day (93.74%) dissolution compared to glibenclamide reference (28.93%). There was no stability issue even after granulation, drying, or at pH 7.4. Thus, glibenclamide dioxane solvate could be an alternative form to improve the molecule’s properties. |
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| Keywords: | solubility glibenclamide solvate dissolution |
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