Stability of cyclophosphamide in lyophilized cakes. II. Urea, polyvinylpyrrolidone, and dextran as excipients
Kovalcik, T.R.; Guillory, J.K.
Journal of Parenteral Science and Technology a Publication of the Parenteral Drug Association 42(5): 165-173
1988
ISSN/ISBN: 0279-7976 PMID: 2462038 Document Number: 755
Lyopilized products containing cyclophosphamide and one of the following excipients: urea, polyvinylpyrrolidone (PVP-40), or dextran, were prepared. All of the products were well-formed cakes. Cyclophosphamide in these lyophilized cakes was found to undergo rapid (t90 < 30 days) degradation in the solid state at room temperature. The lyophilized cakes were humidified with five microliters of water. In the cake containing urea, differential scanning calorimetry, and X-ray diffraction showed that cyclophosphamide was converted from the amorphous to the monohydrate from when exposed to moisture, and exhibited improved stability. In the case of the cake containing PVP-40, the incorporation of moisture resulted in formation of a clear, semi-solid possessing poor stability. The cyclophosphamide/dextran cake remained intact upon humidification. Differential scanning calorimetry and X-ray diffraction showed that cyclophosphamide in this cake was not converted from the amorphous form to the monohydrate form, and exhibited no improvement in stability.
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