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A growing number of co-crystals in the literature are proof of how significant the co-crystallization concept has become. Co-crystallization enhances physicochemical properties through the formation of intermolecular interactions between a drug and a co-former. A co-crystal is a single crystalline material consisting of at least two molecular components solid at room temperature and present in a definite stoichiometric ratio. Pharmaceutical co-crystals consist of the active pharmaceutical ingredient and the co-former selected from generally regarded as safe (GRAS) list of the United State Food and Drug Administration. Co-crystal formation requires an understanding of a drug target, a proper choice of a co-former and is only achieved experimentally after several trials. Other beneficial co-crystallization outcomes include binary eutectics, solid dispersions, amorphous forms, etc. Several key issues including design strategies, co-former selection, and co-crystallization methods; tradition and newly synthetic methods that are more efficient and suitable for large scale have been briefly described. The co-crystal preference is demonstrated with a particular emphasis on multidrug co-crystals and their contribution to the drug combination strategies used for the treatment and management of drug resistance and adverse side effects in serious medical conditions that require the administration of high doses such as HIV/AIDS, tuberculosis, and others. K E Y W O R D S co-crystal development, co-crystallization, design, pharmaceutical co-crystals, preferences, synergistic co-crystals 1 INTRODUCTION Less than 1% of active pharmaceutical ingredients (APIs) reach the market because of poor biopharmaceutical properties among which solubility plays a key role. [1] Poor physicochemical properties of APIs such as chemical stability, dissolution, hygroscopicity, and solubility impact This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
A growing number of co-crystals in the literature are proof of how significant the co-crystallization concept has become. Co-crystallization enhances physicochemical properties through the formation of intermolecular interactions between a drug and a co-former. A co-crystal is a single crystalline material consisting of at least two molecular components solid at room temperature and present in a definite stoichiometric ratio. Pharmaceutical co-crystals consist of the active pharmaceutical ingredient and the co-former selected from generally regarded as safe (GRAS) list of the United State Food and Drug Administration. Co-crystal formation requires an understanding of a drug target, a proper choice of a co-former and is only achieved experimentally after several trials. Other beneficial co-crystallization outcomes include binary eutectics, solid dispersions, amorphous forms, etc. Several key issues including design strategies, co-former selection, and co-crystallization methods; tradition and newly synthetic methods that are more efficient and suitable for large scale have been briefly described. The co-crystal preference is demonstrated with a particular emphasis on multidrug co-crystals and their contribution to the drug combination strategies used for the treatment and management of drug resistance and adverse side effects in serious medical conditions that require the administration of high doses such as HIV/AIDS, tuberculosis, and others. K E Y W O R D S co-crystal development, co-crystallization, design, pharmaceutical co-crystals, preferences, synergistic co-crystals 1 INTRODUCTION Less than 1% of active pharmaceutical ingredients (APIs) reach the market because of poor biopharmaceutical properties among which solubility plays a key role. [1] Poor physicochemical properties of APIs such as chemical stability, dissolution, hygroscopicity, and solubility impact This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This paper describes a new flow-through capillary sample holder that allows the in situ study of re-solvation processes. The holder can be aligned to the goniometer's center using two perpendicular micrometric tables that move in y and z directions. The re-solvation of two ibrutinib solvates of anisole and fluorobenzene was tested using the holder to show the practical application of this technique.
Changes in molecular conformation and its relationship with crystal polymorphism have been well documented in previous work. To the best of our knowledge, however, the effect of solvate formation on molecular conformation has never been explored. Using the Cambridge Structural Database in combination with molecular modeling, we provide insights into the impact of solvate formation on the conformation adopted by a compound and whether such conformation is different to that found in its neat form(s). Typically, the more flexible a molecule is, the higher the chances that conformational change occurs upon solvate formation. There are no trends as to the relative stability of conformers and their likelihood to be observed in either the solvates or the neat forms. Typically, conformer energy differences in solvate-neat form pairs are small (<5 kJ/mol) and when larger energy differences are observed (>15 kJ/mol), these can be reduced significantly when both solvent and thermal effects are considered in the simulations. This highlights of the importance of computing thermal contributions in conformer energies as well as accounting for environmental effects. Overall, we find that conformational change in solvate-neat form pairs mirrors the behavior of conformational change in polymorphism.
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