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Vimon Tantishaiyakul Sarunyoo Songkro Krit Suknuntha Pattakarn Permkum Pattawee Pipatwarakul 《AAPS PharmSciTech》2009,10(3):789-795
We have recently demonstrated that coprecipitation of cimetidine (C) and piroxicam (P) at a mole ratio of 1:1 results in the
transformation of the crystalline forms of both drugs to an amorphous state. In this study, coprecipitates and physical mixtures
of cimetidine and piroxicam were further investigated at C/P mole ratios of 1:10, 1:5, 1:4, 1:2, 10:1, 20:1, 30:1, 40:1, and
52.5:1, the latter being the composition of a clinically used dosage. The physicochemical properties of these samples were
examined using X-ray diffraction and Fourier transform infrared spectroscopy. Additionally, dissolution of piroxicam in the
samples at C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 was investigated at pH 1.2 and pH 4. In coprecipitates with
C/P mole ratios of 10:1, 20:1, 30:1, and 40:1, crystalline forms of both drugs were transformed to amorphous states. A mixture
of an amorphous state and cimetidine crystalline form A was observed for the coprecipitate with a C/P mole ratio of 52.5:1.
For the coprecipitates with C/P mole ratios of 1:2, 1:4, 1:5, and 1:10, cimetidine form A was transformed to form C, whereas
piroxicam form II was modified to form I. It is interesting that small molecules, instead of polymers or solvents, can cause
such crystal structure transformations. The dissolution of piroxicam at pH 4 is lower than that at pH 1.2. Additionally, the
coprecipitates and physical mixtures with C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 demonstrate substantially
higher dissolution of piroxicam compared to that of drug alone. 相似文献
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