Physical characterization and stability of ranitidine and diclofenac amorphous binary system

R. GAITANO; E. V. BRUSAU; E. S. CERUTTI; G. E. NARDA

Córdoba

Congreso; Reunión Internacional de Ciencias Farmacéuticas 2014; 2014

UNC y UNR

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in the symptomatic relief of musculoskeletal or joint pain. The drug is poorly water soluble and several salts are employed in commercial formulations, as is the case of sodium, potassium, diethylamine and pyrrolidine ethanol diclofenac salts. NSAIDs are well known to cause side effects including gastrointestinal disturbances. Ranitidine hydrochloride, a H2-receptor antagonist, is widely used in the treatment of stomach ulcer and to counteract gastric irritation resulting from NSAID treatment. It is therefore reasonable to co-administer these drugs in a single formulation. The binary system was prepared by co-precipitation of ranitidine hydrochloride and sodium diclofenac in water in a ratio similar to that of their therapeutic daily dose. Fourier-transform infrared spectroscopy evidenced that both active pharmaceutical ingredients (APIs) are present in the spectrum of the obtained solid; the characteristic frequencies of those functional groups, able to form the necessary supramolecular synthons, showed slight shifts. Further confirmation was obtained by tandem mass spectrometry. The solid demonstrated to be amorphous according to its powder X-ray diffraction pattern and remained stable in that condition up to three months during storage at 20 °C. Thermogravimetric analysis indicated the sample starts decomposition at 145 °C. Besides, an endothermic event consistent with a fusion process at 104 °C ? well below the corresponding ones for each API ? was observed in the differential scanning calorimetry curve, after a weak signal. These results seem promising for exploring the solubility properties of this binary system.