期刊
PHARMACEUTICAL RESEARCH
卷 23, 期 10, 页码 2375-2380出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-006-9045-y
关键词
flufenamic acid; mefenamic acid; polymorph selection; single crystal; XRPD
Purpose. To utilize additives to develop a strategy and a method to grow single crystals that allow structure determination of a metastable form of a drug. Materials and Methods. The metastable form of mefenamic acid (MFA) was grown in the presence of various amounts of the structurally similar additive flufenamic acid (FFA) in ethanol. Single crystal X-ray analysis was performed on the single crystals of MFA II that were formed. The solubility of MFA in the presence of FFA was measured to elucidate the mechanism of MFA II formation. Results. A supersaturated solution of MFA in ethanol produced the metastable form using FFA as an additive. Ethanol-water mixtures and toluene were also used to investigate the relationships between form produced and solvent since these two solvent systems do not produce MFA II. Conclusions. Additives can be used to obtain the metastable form of pharmaceutical compounds, and the relationships between molecules and solvent as well as between host and guest molecules are critical to obtaining the desired form.
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