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The check of the solid phase in which the active principles crystallize is an activity of primary importance, both in the preformulation studies and in the quality control of pharmaceutical products. Indeed, it is necessary to ensure that only the polymorph of interest is present in the dosage form, as well as in the various stages leading to its preparation. The regulatory agencies underline the importance of limiting the presence, in the pharmaceutical solids, of polymorphic impurities which, having different physico-chemical, technological and pharmaceutical properties, could compromise the efficacy, the stability and the safety of the product. The present work fits into this problem and is configured as a response to the industrial need to identify the presence of an unwanted polymorph in batches of powder of an active ingredient, also in systems in which these determinations show serious problems. In particular, the studies here performed respond to the need to develop a method that allows to detect and quantify the presence of polymorphic impurity in dexketoprofen trometamol samples by the DSC technique. The main critical points of this system are constituted by the fact that the melting enthalpies of the two polymorphs (A and B) are very similar and the difference between the onset temperatures of their melting is just 2 °C. This second point makes it impossible to obtain an adequate resolution of the melting peaks, even when the experimental conditions are appropriately selected. A system characterized by this thermal behavior, in the scientific literature, is considered "impossible". The success of the method developed in this work is to be attributed, on the one side, to the methods adopted in the preparation of the physical mixtures of the two polymorphs, which need to have the composition as homogeneous as possible, and on the other side, to the idea of performing a conditioning of the samples that makes the low-melting temperature polymorph thermally inert. The polymorphic mixtures treated in this way show only the fusion of the high-melting temperature polymorph whose enthalpy decreases linearly with the increase of impurity present in the mixture. The method proposed here allows to detect the polymorphic impurity even when it is present in a very low percentage, equal to 0.3, while it is possible to quantify it reliably for contents higher than 2%. [ABSTRACT FROM AUTHOR]

The eco-friendly method of kneading was here used to synthesize a cocrystal of probenecid, an uricosuric drug used in treating gout and hyperuricemia, with the aim to improve its pharmaceutical behavior. Benzamide was selected as a co-former showing functional groups favorable to the formation of supramolecular synthons with the active principle. The kneading product was characterized by a range of experimental techniques (microscopic, spectroscopic, thermal and diffractometric) all proving the formation of the new multicomponent crystal. In particular, the FT-IR and NMR techniques showed that an important change of hydrogen bonds network takes place in the kneading product and that the acid–acid interaction in the pristine drug is replaced with the related acid-amide one in the cocrystal. The cocrystal solubility and dissolution rate measured in several biorelevant fluids showed an actual improvement with respect to the pure drug. [ABSTRACT FROM AUTHOR]

The aim of this work was to search for new polymorphic forms of febantel, an anthelminthic drug of great present interest for the veterinary industry. Solvent-based recrystallization, thermal and mechanical treatments and spray drying were chosen to discover new solid forms. The solids obtained were physicochemically characterized by thermal techniques (DSC and TG), FTIR spectroscopy, laboratory and synchrotron X-ray powder diffraction and scanning electron microscopy. Our work leads to obtain a new solid form never described in the literature. In particular, the new polymorph was obtained by the anti-solvent method and the crystallization from isopropanol. The experimental conditions of crystallization favorable to the formation of the highest amount of the new solid phase were selected. The new phase shows a thermal, spectroscopic and diffractometric behavior unique. Furthermore, the preliminary structure investigation suggests two possible crystal systems: an orthorhombic or a monoclinic one, with really comparable lattice parameters and cell volume. Measurements put into evidence that the new phase is a metastable polymorph that is in monotropic relationship with the stable and known form. [ABSTRACT FROM AUTHOR]