FIELD: pharmacology.
SUBSTANCE: invention relates to new crystalline forms of sodium salt or sodium salt monohydrate of a compound of the general formula (AA). The compound has inhibitory activity against HIV integrase. The AA compound corresponds to the following structural formula:
.
The crystalline form of the sodium salt of the AA compound has (a) characteristic diffraction peaks at 2-theta angles of 6.4±0.2°; 9.2±0.2°; 13.8°±0.2°; 19.2±0.2° and 21.8°±0.2°, in the X-ray powder diffraction pattern and/or (b) the characteristic infrared absorption spectra at 1641 cm-1 ± 2 cm-1, 1536 cm-1 ± 2 cm-1, 1503 cm-1 ± 2 cm-1 and 1424 cm-1 ± 2 cm-1 and/or (c) 13C-NMR spectra in the solid state, substantially as shown in Fig. 3. The crystalline form of the sodium salt monohydrate of the AA compound has (d) characteristic diffraction peaks at 2-theta angles equal to 8.0°±0.2°; 9.3°±0.2°; 11.3°±0.2°; 16.0°±0.2° and 22.8°±0.2°, in the X-ray powder diffraction pattern and/or (e) characteristic infrared absorption spectra at 1637 cm-1 ± 2 cm-1, 1536 cm-1 ± 2 cm-1, 1501 cm-1 ± 2 cm-1 and 1422 cm-1 ± 2 cm-1 and has substantially X-ray diffraction patterns, as shown in Fig. 4. The invention also relates to a pharmaceutical composition comprising the said crystalline forms, as well as to a process for preparation of the crystalline form of the sodium salt monohydrate of the AA compound. The method includes stages: a) dissolution of the sodium salt compounds of the formula (AA) in a solution of THF (tetrahydrofuran)-water, b) addition of aqueous NaOH to the obtained solution, c) stirring of the obtained mixture, d) filtering of the obtained sediment, washing it with a THF solution - water and THF and drying.
EFFECT: crystalline forms of the sodium salt and its monohydrate show high solubility in water or saline, have high bioavailability, increased stability to heat and light, and simplify compound application.
13 cl, 7 dwg, 3 ex
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