Complex Formation with Layered Double Hydroxides for the Remediation of Hygroscopicity

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  • Hayashi Aki
    Department of Functional Molecular Chemistry, Kobe Pharmaceutical University
  • Kubota Mai
    Department of Functional Molecular Chemistry, Kobe Pharmaceutical University
  • Okamura Miki
    Department of Functional Molecular Chemistry, Kobe Pharmaceutical University
  • Nakayama Hirokazu
    Department of Functional Molecular Chemistry, Kobe Pharmaceutical University

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Layered double hydroxides (LDHs) have been used commercially as antacids, to stabilize drugs, to allow the controlled release of incorporated drugs, and to act as drug carriers to reduce drug accumulation within the body. Several types of LDH were investigated: nitrate type (LDH-NO3); chloride type (LDH-Cl); and carbonate type (LDH-CO3). Each type was added to an aqueous or methanol (MeOH) solution containing a drug (pravastatin or nateglinide). With pravastatin sodium, the interlayer distance expanded after reaction with LDH-NO3 and LDH-Cl in aqueous solution. In contrast, the interlayer distance of LDH-CO3 increased in methanol with nateglinide. Each drug was intercalated into the interlayer space of LDH by ion exchange. The hygroscopicity of the drug substances, complexes, and physical mixtures were determined at 70% relative humidity. Increases in weight (%) of the complexes were less than those of the physical mixtures, which demonstrates that hygroscopicity was reduced upon complexation with LDH due to the layer of LDH over the drugs.

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