Sodium ibuprofen dihydrate and anhydrous Study of the dehydration and hydration mechanisms Roberta Censi • Valentina Martena • Ela Hoti • Ledjan Malaj • Piera Di Martino Received: 12 October 2011 / Accepted: 3 January 2012 / Published online: 4 February 2012 Ó Akade ´miai Kiado ´, Budapest, Hungary 2012 Abstract (R,S)-(±)-ibuprofen sodium salt (racemate) dihydrate (SID) was dehydrated and the physicochemical properties of SID and the anhydrous forms (SIA) were com- pared by different analytical techniques (scanning electron microscopy, helium pychnometry, differential scanning cal- orimetry, X-ray powder diffractometry). The dehydration of SID, followed by thermogravimetry in isothermal conditions, allowed to calculate the activation energy of the dehydration process and to predict the mechanism of dehydration. Dehy- dration occurred in one step and the activation energy was rather low, indicating the ease of water removal from the crystal. The mechanism of dehydration followed a three dimensional diffusion (Jander equation). Similarly to the dehydration, the hydration process was followed under iso- thermal conditions by exposing the anhydrous powder at 64% RH at different temperatures. The mechanism of hydration was governed by a two dimensional diffusion and the energy associated to the process was very low, indicating the ease of crystal hydration. The driving force for the hydration is higher than that for the dehydration. From a thermodynamic point of view this fact may explain why the hydrated form is more stable than the anhydrous one. Solubilities, determined at different temperatures in water and in phosphate buffer (pH 6.8), showed that SID is more soluble in water than SIA for temperatures higher than approximately 283 K. On the contrary, in phosphate buffer SIA is always more soluble than SID in the temperature range considered for the experiments. Drug release reflects the solubility in water and phosphate buffer previously reported. Keywords Sodium ibuprofen  Hydration  Dehydration  Activation energy  Solubility  Dissolution Introduction Knowledge of hydration and dehydration behavior of drugs is fundamental for developing stable pharmaceutical for- mulations and predicting appropriate storage conditions for drugs and solid dosage forms [1]. This is particularly important because changes in drug physicochemical prop- erties may differently affect its biopharmaceutical or technological properties. In general, increasing degrees of hydration results in lower dissolution rates. This is for example the case of carbamazepine dihydrate that showed lower dissolution behavior and bioavailability than the corresponding anhydrous polymorphs I and III [2]. Similar results were reported for theophylline [3], ampicillin [4], and oxyphenbutazone [5]. Exceptions to this behavior were also reported, as in the case of erythromycin [6]. Also from a technological point of view, hydration/dehydration phenomena may strongly affect the drug properties. For example, p-hydroxybenzoic acid showed improved tablet- ing properties in its monohydrate form as compared to the anhydrous one [7]. Similarly, sodium naproxen exhibited higher compressibility properties when it is converted from its anhydrous form to its superior hydrates [8, 9]. Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), is a well-accepted and well-documented analgesic for the treatment of pain as self-medication and has been proven to be R. Censi  V. Martena  P. Di Martino (&) School of Pharmacy, University of Camerino, Via S. Agostino, 1, 62032 Camerino, Italy e-mail: piera.dimartino@unicam.it E. Hoti  L. Malaj Department of Pharmacy, University of Tirana, Street of Dibres, Tirana, Albania 123 J Therm Anal Calorim (2013) 111:2009–2018 DOI 10.1007/s10973-012-2194-9