کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8514188 1556504 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Pressure-Temperature Phase Diagram of Metacetamol and Its Comparison to the Phase Diagram of Paracetamol
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
The Pressure-Temperature Phase Diagram of Metacetamol and Its Comparison to the Phase Diagram of Paracetamol
چکیده انگلیسی
Understanding the polymorphic behavior of active pharmaceutical ingredients is important for formulation purposes and regulatory reasons. Metacetamol is an isomer of paracetamol and it similarly exhibits polymorphism. In the present article, it has been found that one of the polymorphs of metacetamol is only stable under increased pressure, which has led to the conclusion that metacetamol like paracetamol is a monotropic system under ordinary (= laboratory) conditions and that it becomes enantiotropic under pressure with the I-II-L triple point coordinates for metacetamol TI-II-L = 535 ± 10 K and PI-II-L = 692 ± 70 MPa. However, whereas for paracetamol the enantiotropy under pressure can be foreseen, because the metastable polymorph is denser, in the case of metacetamol this is not possible, as the metastable polymorph is less dense than the stable one. The existence of the stability domain for the less dense polymorph of metacetamol can only be demonstrated by the construction of the topological phase diagram as presented in this article. It is a delicate interplay between the specific volume differences and the enthalpy differences causing the stability domain of the less dense polymorph to be sandwiched between the denser polymorph and the liquid. Metacetamol shares this behavior with bicalutamide and fluoxetine nitrate.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 6, June 2017, Pages 1538-1544
نویسندگان
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