Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Characterization of the Physicochemical Properties of KR-31378

  • Published : 2003.07.01
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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 n-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, $60^{\circ}C$. The stability testing indicated that the t90 for the drug in solid was estimated to be 2 years and 128.6 days at $25^{\circ}C$, while the that in aquesou solution was 68.6 days at $25^{\circ}C$. 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 $\mu$ m with the mean particle size of 37.9 $\mu$ m. 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 $37^{\circ}C$ in water.

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