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  • Title: Effect of seed crystals on solid-state transformation of polymorphs of chloramphenicol palmitate during grinding.
    Author: Otsuka M, Kaneniwa N.
    Journal: J Pharm Sci; 1986 May; 75(5):506-11. PubMed ID: 3735092.
    Abstract:
    The polymorphic transformations of chloramphenicol palmitate, (2R, 3R)-2-(2,2-dichloroacetamido)-3-hydroxy-3-(4-nitrophenyl) propyl palmitate (1), during grinding in an agate centrifugal ball mill at 200 rpm, and the effect of seed crystals on the transformation were studied by means of X-ray diffraction analysis, differential scanning calorimetry, and scanning electron microscopy. The transformation was analyzed using the kinetic method based on nine kinetic model equations. Form B of 1 was transformed to form A (the therapeutically least active form) during grinding for more than 150 min, but in the presence of 1% of form A as seed crystals, form B was transformed to form A during grinding for 40 min. The transformations of form B during grinding in the absence and in the presence of seed crystals were fitted to the two-dimensional nuclear growth equation (Avrami equation). Form C was transformed to form B during grinding for 16 min (and then to form A when grinding was continued for a total of 160 min). The transformation of form C to form B during grinding was accelerated by the presence of 1% of form B, while the subsequent transformation to form A was unaffected, as expected. On the other hand, in the presence of 1% of form A, both the transformation of form C to form B and the subsequent transformation to form A were completed within a grinding time of only 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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