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Characterization of the physicochemical properties of KR-31378

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Abstract

KR-31378 is a new drug candidate intended for the use in the prevention of ischemia-reperfusion damage. The objective of this preformulation study was to determine the physicochemical properties of KR-31378. The η-octanol to water partition coefficients of KR-31378 were 0.0504 at pH 3 and 0.8874 at pH 10. Accelerated stability of KR-31378 in solution and solid state was studied at 5, 40, 60°C. The stability testing indicated that thet90 for the drug in solid was estimated to be 2 years and 128.6 days at 25°C, while the that in aquesou solution was 68.6 days at 25°C. The KR-31378 was also found to be unstable under the relative humidity of 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of KR-31378 with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1:1 binary mixtures of KR-31378 and Aerosil, Avicel, Eudragit, lactose, PEG, talc, CMC, PVP, starch. As a result, CMC, PVP, and starch were found to be incompatible with KR-31378, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of KR-31378 powder was in the size range of 9–93 μm with the mean particle size of 37.9 μm. The flowability of KR-31378 was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Crystallization of the drug with a number of organic solvents did not lead a crystalline polymorphism. In addition, dissolution of the drug from the powder was adequately rapid at 37ΰC in water.

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Authors and Affiliations

  1. College of Pharmacy, Duksung Women’s University, 132-714, Seoul, Korea

    Young Taek Sohn & Bo Ye Park

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  1. Young Taek Sohn
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  2. Bo Ye Park
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Correspondence to Young Taek Sohn.

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Sohn, Y.T., Park, B.Y. Characterization of the physicochemical properties of KR-31378. Arch Pharm Res 26, 526–531 (2003). https://doi.org/10.1007/BF02976875

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  • DOI: https://doi.org/10.1007/BF02976875

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