Abstract
Salt formation has been known to improve some physicochemical properties of active pharmaceutical ingredients particularly solubility. In this study, mefenamic acid (MA) formed salts with ethylenediamine (EDM), triethylamine (TA), 1-methylpiperazine (MP), and morpholine (MOP). In the salt structures studied, the proton of the carboxylic acid group of the MA molecule was transferred to a nitrogen atom of the amine. Both crystal structures of the ethylenediammonium and morpholinium salts were solved successfully by single-crystal X-ray diffraction in the space group PĪ. The triethylammonium and the 1-methylpiperazinium salts solved in Pbca and P21/c, respectively. The thermal behavior of the salts was investigated, and the desolvated powders were analyzed using powder X-ray diffraction. Grinding and slurry experiments were also investigated as alternate methods for preparation of the salts. The desolvation experiments yielded interesting results with the desolvation of (MA−)(MP+) resulting in MA form I, desolvation of (MA−)(TA+) gave mixtures of MA form I and MA form II, whereas desolvation of (MA−)(MOP+) gave MA form II. The solubility trend in water was determined as (MA−)(MP+) > (MA−)(TA+) > (MA−)(MOP+) > (MA−)(EDM+), with (MA−)(MP+) the most-soluble and (MA−)(EDM+) the least-soluble salt.
Original language | English |
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Pages (from-to) | 3014-3021 |
Number of pages | 8 |
Journal | Journal of Pharmaceutical Sciences |
Volume | 107 |
Issue number | 12 |
DOIs | |
Publication status | Published - Dec 2018 |
Externally published | Yes |
Keywords
- crystal engineering
- crystal structure
- desolvation
- mefenamic acid
- solubility
- thermal analysis
- thermogravimetric analysis