Forced degradation of tacrolimus and the development of a UHPLC method for impurities determination.

An ultra-high performance liquid chromatography method for simultaneous determination of tacrolimus impurities in pharmaceutical dosage forms has been developed. Appropriate chromatographic separation was achieved on a BEH C18 column using gradient elution with a total run time of 14 min. The method was applied to analyses of commercial samples and was validated in terms of linearity, precision, accuracy, sensitivity and specificity. It was found to be linear, precise and accurate in the range of 0.05 to 0.6 % of the impurities level in pharmaceutical dosage forms. Stability indicating power of the method was demonstrated by the results of forced degradation studies. The forced degradation study in solution revealed tacrolimus instability under stress alkaline, thermal, light and photolytic conditions and in the presence of a radical initiator or metal ions. The drug was stable at pH 3-5. Solid-state degradation studies conducted on amorphous tacrolimus demonstrated its sensitivity to light, elevated temperature, humidity and oxidation.

Bis{(R)-1-(3-amino-sulfonyl-4-meth-oxy-phen-yl)-N-[2-(2-eth-oxy-phen-oxy)eth-yl]propan-2-aminium} adipate tetra-hydrate.

The title compound, 2C20H29N2O5S(+)·C6H8O4 (2-)·4H2O, which was found to be optically active, is a relatively rare example of a chiral compound crystallizing in the triclinic crystal system. The dihedral angles between the phenyl rings of the cations are 60.03 (15) and 62.03 (16)°, while the C atoms of the anion are almost coplanar (r.m.s. deviation 0.085 Å) and all trans to each other. In the crystal, the components are connected by an extensive network of N-H⋯O and O-H⋯O hydrogen bonds. The sulfonamide groups link the cations into pairs via two N-H⋯O hydrogen bonds about the pseudo-inversion centre, leading to the formation of R 2 (2)(8) rings. The anions are stacked in between four cationic pairs. Pairs of water mol-ecules bridge the larger building units, forming hydrogen bonds with the remaining two O atoms of the anion.

A novel crystal form of cabergoline, form L.

A new crystal form of cabergoline, form L, was discovered and characterized by thermal analyses, X-ray powder diffraction (XRPD), infrared spectroscopy (IR), Raman spectroscopy, dynamic vapor sorption (DVS), and comparative dissolution behavior. The morphology of rod-shaped crystals was investigated by scanning electron microscopy (SEM). Form L was compared to other non-solvated forms of cabergoline such as form I, II, VII and to the amorphous form. The thermodynamic stability of form L is supported by its long-term stability. Form L is a pharmaceutically applicable crystal form.