Hydrate modifications of the non-steroidal anti-inflammatory drug diclofenac sodium: Solid-state characterisation of a trihydrate form

Abstract

Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used in painful and inflammatory diseases. It can exist in different hydrate phases. By exposure to different conditions of temperature and relative humidity can be isolated a trihydrate form never described in literature. The methods of preparation of the trihydrate form (named DSH3) were described and its physico-chemical properties were investigated. Data from FTIR spectroscopy, X-ray powder diffraction and thermal analysis were used for identification and characterisation of DSH3 in comparison with the anhydrous form (DS, the commercial form) and the hydrate form DSH (obtained by exposure of DS to relative humidity even below 60% and already described and characterised in a previous article of the same authors). Intrinsic dissolution studies were performed to compare the pharmaceutical properties of DS and DSH with DSH3, since this form was accidentally found on the Italian market as active pharmaceutical ingredient (API). This work stresses the importance of assessing the correct crystalline form also in API of well-established use to guarantee quality, safety and efficacy of the final dosage form. Furthermore, this study suggests that isomorphic hydrate forms with a different dislocation of water within the crystal structures can exist.