A new dosage form of emodin: For solubility and dissolution rate enhancement and application in Alzheimer's disease and bacteriostasis

Emodin (EM), with two pKa values (pKa1 = 8.0 and pKa2 = 10.9), presents low solubility and dissolution rate, which results in low bioavailability. In this report, two EM sodium salts, C15H9−O5·Na+C15H9O5−·Na+ (EM-1Na) and C15H8O52−·2Na+C15H8O52−·2Na+ (EM-2Na), were prepared by adding various amounts of sodium hydroxide. Salt forms were characterized by FT-IR, XRPD, 1H NMR, DSC, and SEM, as well as solubility and dissolution rate studies in triple-deionized water, buffer at pH 1.2 and pH 6.8, respectively. The aqueous solubility of EM was notably enhanced by more than 20,000 and 50,000 times, corresponding to EM-1Na and EM-2Na. Meanwhile, the dissolution rate exhibited significant enhancement and the dissolution time was shortened. The results showed the dissolution of EM-1Na and EM-2Na was 25 and 35 times greater than EM in 60 min. The results of β-amyloid (Aβ) self-aggregation inhibition and MIC assay did not show apparent difference from those of EM, indicating that the functional groups were not broken down. Moreover, salt formation significantly enhanced the bioavailability of EM, consistent with the ABTS free radical scavenging test results. The significant decrease in IC50 values in the range of 18,394 μg/mL to 29.07 μg/mL indicated a more effective anti-AD action.

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