This is probably because of differences in the structural changes (e.g., intermolecular distance) that occur in each type of crystal when the temperature changes. 2019 Oct;9(5):339-346. doi: 10.1016/j.jpha.2019.07.001. Garti N(1), Libster D, Aserin A. Mihoko Maruyama, ... Yusuke Mori, in Kinetic Control in Synthesis and Self-Assembly, 2019. Poly(3-methyl-1-butene) possesses two crystalline forms: monoclinic and pseudo-orthorhombic. 2004 Feb 23;56(3):275-300. doi: 10.1016/j.addr.2003.10.020. This review highlights the pervasiveness and relevance of polymorphism and describes solid form screening and selection processes. Heliyon. 7. J Pharm Anal. However, since these excipients often have their own THz absorption spectra, identifying them is also an important issue. These crystal changes have severely restricted the commercial potential of poly(1-butene). Inconsistencies in the solid phase produced during the manufacturing and storage of drug substances and drug products may have severe consequences. 2009 Jan;71(1):23-37. doi: 10.1016/j.ejpb.2008.07.014. Copyright © 2021 Elsevier B.V. or its licensors or contributors. Isotactic poly(1-butene) crystallizes in the metastable, tetragonal form II, which converts over time (storage time of days or weeks) to the trigonal form I, with a volume contraction. Transformations from one phase to another may indeed be spontaneous and reversible or not. One reversible example is the transformation, near room temperature, of polytetrafluoroethylene (PTFE) from a 157 to 136 helical conformation. Polymorphism in Molecular Crystals The three-dimensional arrangement of drug molecules in the solid state is of critical importance to physical properties such as solubility and bioavailability. Crystals, an international, peer-reviewed Open Access journal. To these can be added theoretical techniques, developed more recently, and aimed at the prediction of the crystal structures of new polymorphs, as well as their morphologies. The search for crystal polymorphism of pharmaceutical compounds is important from the identification of crystal polymorphism and the contribution to the development of more effective pharmaceuticals. More recently, Urakami reviewed the use of isothermal calorimetry for estimating enthalpies of solution and transition of pharmaceutical polymorphs [4]. Form I is thermodynamically the most stable, but form II is the form produced on cooling from the melt. 2007;59:617–30. This refers to the crystallization of a compound in different forms that arise directly as a result of isotopic substitution (e.g., one or more 1H atoms in the molecule are replaced by deuterium).29 It is assumed here that the use of the term should be justified only in instances where it is clearly demonstrated that the particular isotopic substitution employed is exclusively responsible for the occurrence of the two crystals. Dear Colleagues, Polymorphism, as a ubiquitous phenomenon where the same chemical entities comprise different solid-state architectures by virtue of their different spatial arrangement and intermolecular connectivity, has been intriguing scientists for more than a century. (2014 The Electrochemical Society, with alterations). However, we have found that if the temperature is reduced inside an environmental control chamber, it is possible to separate the three substances—famotidine-A, famotidine-B, and d-mannitol in an image. Araya-Sibaja AM, Maduro de Campos CE, Fandaruff C, Vega-Baudrit JR, Guillén-Girón T, Navarro-Hoyos M, Cuffini SL. It also shows a set of THz absorbance images at 1.07 and 1.65 THz obtained after calibration with an image at 0.8 THz. Vavilova AA, Padnya PL, Mukhametzyanov TA, Buzyurov AV, Usachev KS, Islamov DR, Ziganshin MA, Boldyrev AE, Stoikov II. However, it is often difficult to distinguish them from excipients. Polymorphism in molecular crystals is a prevalent phenomenon and is of great interest to the pharmaceutical community. In crystalline form a solid can exist as polymorph, hydrate, solvate, or co-crystal. These may be solvent … Inconsistencies in the solid phase produced during the manufacturing and storage of drug substances and drug products may have severe consequences. Form II then transforms to form I, a process which takes several days at ambient temperatures. This new, more thermodynamically stable polymorphic form had very different physical properties than the earlier material and Abbott was forced to withdraw the drug from sale. Would you like email updates of new search results? Aaltonen J, Allesø M, Mirza S, Koradia V, Gordon KC, Rantanen J. Eur J Pharm Biopharm. Generation of a specific crystal phase necessitates an intimate knowledge of the “crystal phase diagram” of any polymer, with thermal treatments, solvents, processing conditions, etc. CRYSTAL POLYMORPHISMIt has been recognized that crystal polymorphism is an important factor related to the physicochemical and biological properties of drug substances and formulations. Author information: (1)The Ratner Chair in Chemistry, Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel. Then new methods for selective crystallization of the metastable phase will be introduced: crystallization with cavitation bubbles induced by femtosecond laser irradiation or ultrasonic irradiation and polymer-induced heteronucleation. Polymorphism in molecular crystals is a prevalent phenomenon and is of great interest to the pharmaceutical community. The chapter reviews polymorphic interconversion and phase transitions. The crystal polymorphism of polymers is a structural variable which may be detrimental or favorable, as it offers a possibility to tailor the properties of the material. Raman Microspectroscopy as a Tool to Elucidate the Efficacy of Topical Formulations Containing Curcumin. Lipid polymorphism in lyotropic liquid crystals for triggered release of bioactives. Irbesartan desmotropes: Solid-state characterization, thermodynamic study and dissolution properties. Iermak I, da Silva AP, Kurachi C, Bagnato VS, Inada NM. Since the over-the-counter tablet mainly contained form B, the absorbance of the image at 1.07 is much larger than that of the 1.65 THz image. Further details are provided in a forthcoming section. Famotidine, a constituent of some stomach medicines, exhibits crystal polymorphism between a low-solubility type A and a high-solubility type B. Some of the easiest methods to generate metastable phases of a given polymer (such as e.g., the β phase of iPP) involve the use of nucleating agents (cf. The next section of this chapter describes significant recent developments in research on crystal polymorphism, with an emphasis on new methods of producing polymorphs because this has important implications for their rapid characterization by analytical methods. In this chapter, describing the use of thermal methods of analysis to investigate polymorphism, information gleaned from complementary techniques will therefore also feature. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 2019 Mar 23;12(1):44. doi: 10.3390/ph12010044. High-resolution 13C CPMAS solid-state NMR experiments have successfully been used to assess crystal polymorphism in lipids, which is an important feature for explaining and understanding melting behavior of, for example, chocolate and margarines. The solid-state form is a key quality attribute of a crystalline product. The structure of the solid crystal is essential to determine the effectiveness of the drug and the effects it can have on the body. Curr Opin Drug Discov Devel. Our polymorphism screening strategy has been optimized through decades of experience and is readily tailored to our customers’ needs. The image acquisition time for the tablet was about 3 h with a 0.2 mm spatial resolution. Crystal polymorphism is the phenomenon whereby crystals formed by the same kinds of molecules can take different forms depending on the intermolecular arrangements. Crystal Polymorphism in Dolutegravir Sodium: Application of 3D-Precession Diffraction Tomography Amit Singh1, Ram K R Jetti1, Partha P Das2, S Nicolopoulos2 1Chemical Research Division, API-R&D, Mylan Laboratories Limited, Hyderabad, India, 2NanoMEGAS SPRL, Brussels, Belgium E-mail: Dolutegravir sodium is a BCS Class II drug which is being developed for the … NIH NLM To a large extent, this holistic approach to the study of crystal polymorphism has been driven by regulatory bodies responsible for ensuring robust manufacture, safety and efficacy of pharmaceutical products [1]. Fig. The major section of this chapter will describe recent case studies illustrating the use of thermal methods and complementary techniques to identify polymorphs and clarify thermodynamic relationships in polymorphic systems. COVID-19 is an emerging, rapidly evolving situation. Cryst Growth Des. The frequency-dependent images clearly show the molecular distribution of famotidine form B and other chemicals in the tablet for the first time. DSC technology coupled with XRD, Raman spectroscopy and thermomicroscopy. Get the latest public health information from CDC:, Get the latest research information from NIH:, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: Although high-resolution NMR methods provide less detailed information at the molecular level, 1H NMR relaxometry is still a convenient and quantitative tool for overall assessment of crystallization and ordering phenomena in foods. It covers all important issues by way of case studies, ranging from properties and crystallization, via thermodynamics, analytics and theoretical modelling right up to patent issues. This interest stems from the fact that two of its phases (the β phase and the so-called “poled α phase”) are piezoelectric. For the practical use of metastable phase of pharmaceutical compounds, high stability is extremely important and needed. Caira, in Comprehensive Supramolecular Chemistry II, 2017. Furthermore, these properties are brought about only when the phases are properly oriented in the device: both crystal structure and impact of processing conditions need to be mastered to take advantage of the crystal polymorphism. Poly(4-methyl-1-pentene) possesses tetragonal crystals. Phipps has also treated applications of isothermal microcalorimetry techniques in the pharmaceutical setting [5] emphasizing their use in studying drug polymorphic transformations, as well as in the detection of low levels (<1%) of amorphous phases on the surfaces of crystal polymorphs. 8. 2020 Sep 2;20(9):6069-6083. doi: 10.1021/acs.cgd.0c00777. In this instance, the authors of the study concluded that “configurational polymorphism” was not an appropriate descriptor, given the facile interconversion of the configurations in solution. 3) and felodipine (10, Fig. Pharmaceuticals (Basel). The ubiquity of crystal polymorphism, coupled with novel methodology for generating polymorphs, high-throughput polymorph isolation, and increasing regulatory demands on the need for control of crystallized forms in many areas of solid-state chemistry, presents on-going challenges in the identification of new polymorphs and their comprehensive structural and thermal characterization. 2D Monomolecular Nanosheets Based on Thiacalixarene Derivatives: Synthesis, Solid State Self-Assembly and Crystal Polymorphism. 2006 Nov;9(6):806-15. It is essential to understand the solid-state … The resulting dimensional instability of molded parts is unacceptable; means to produce form I directly include the addition of comonomers or the use of specific nucleating agents for form I (cf. "Effect of temperature and solvent of solvent-mediated polymorph transformation on ASP3026 polymorphs and scale-up" Organic Process Research and Development (2016), 20, 5, 970-976. Crystal Growth & Design 2014 , 14 (4) , 2056-2072. Polymorphism, a common phenomenon in small molecule drug substances, refers to a compound's ability to have different crystal structures and hence different physical properties such as solubility, chemical stability, melting point, density, etc. The polymorphism of the excipients may also play an important role in bioavailability. In a complementary manner, information on the existence and nature of ordered and amorphous domains can be obtained using stable nitroxide-based radical probes that produce ESR signals that are very sensitive to ordering phenomena. 3D energy frameworks of dimethylbenzophenone tetramorphs. High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids. Color polymorphism is an interesting property of chemical systems which present crystal polymorphs of different colors. Mutalik S, Prambil A, Krishnan M, Achuta NU. These results demonstrate that THz spectroscopic imaging is a unique and powerful tool for obtaining the distribution of different polymorphic forms of molecular crystals in opaque samples, which is useful as a pharmaceutical evaluation technique. This site needs JavaScript to work properly. Small organic molecules often exhibit an amazing polymorphism. Cocrystals of carbamazepine with nicotinamide and saccharin are shown to be polymorphic. Inconsistencies in the solid phase produced during the manufacturing and storage of drug substances and drug products may have severe consequences. Specialised, high-speed DSC techniques for the characterization of drug polymorphs and TG for drug hydrate analysis have been reviewed by Sichina [7]. Many molecular crystals are capable of solidifying in multiple crystalline forms. The Eight Hydrates of Strychnine Sulfate. In the summer of 1998, supplies of the drug were interrupted by the appearance of a new crystal form (polymorphism) at a plant in the USA and then later at a plant in Italy. An important focus in pharmaceutical research has been on controlling the drug form to improve the solubility and thus bioavailability of APIs. This can result in large variations in the effectiveness of medicines due to differences in chemical properties such as solubility. Polymorphism is a solid-state phenomenon and is the ability of an element or compound to exist in more than one crystalline form. It is essential to understand the solid-state … Polymorphism is the ability of solid materials to exist in two or more crystalline forms with different arrangements or conformations of the constituents in the crystal lattice. Fig. Polymorphism is a common phenomenon of crystalline materials. Proper monitoring by appropriate physicochemical and/or processing conditions is therefore mandatory. doi: 10.1016/j.heliyon.2019.e01209. [Advances in the quantitative analytical methods of drug polymorphism]. doi: 10.1146/annurev-chembioeng-061010-114224. The two helices are nearly isosteric, and reverse conversion takes place on changing the temperature. Polymorphism in molecular crystals is a prevalent phenomenon and is of great interest to the pharmaceutical community. We review the polymorphism of p -aminobenzoic acid (p ABA), a model drug compound whose crystallisation and polymorphic behaviour has been extensively studied in recent years.