Graciela Díaz de Delgado

SMCr. VIII Congreso Nacional de Cristalografía
II Reunión Latinoamericana de Cristalografía
VI Reunión de Usuarios de Luz Sincrotrón
23-27 de octubre del 2016. Mérida, Yucatán, México
Characterization of Active Pharmaceutical
Ingredients (APIs), New Solid Forms of APIs
and of Organic and Metal Derivatives of APIs
Graciela Díaz de Delgado*.
1
Laboratorio de Cristalografía-LNDRX, Departamento de Química, Facultad de Ciencias, Universidad
de Los Andes, Mérida, 5101, Venezuela.
*e-mail: [email protected]
Abstract. The characterization of several Active Phramaceutical Ingredients (APIs) isolated from
comercial formulations will be presented in this contribution. Additionally, several examples of new
forms of common APIs and of derivatives obtained under different crystallization conditions will be
discussed. The structural characterization of these materials has been carried out by single crystal and
powder diffraction techniques using conventional X ray sources as well as synchrotron radiation.
Key words: Active Pharmaceutical Ingredients, Polymorphism, Single crystal X ray Diffraction,
Powder X ray Diffraction, Synchrotron radiation.
Texto. An important number of Active Pharmaceutical Ingredients (API) are crystalline solids. This makes it
easier to characterize by common solid state techniques and to formulate in solid forms such as tablets, powders,
capsules, etc. However, synthetic procedures and changes during manufacture, transport, and storage may induce
structural changes which could influence the performance of the API. The formation of new polymorphs,
solvates, anhydrates, decomposition products, organic or metal derivatives, among other possibilities, will
influence significantly the behavior of the API. Therefore, studies of APIs under different crystallization
conditions, temperature, solvent, humidity, pressure, light, etc. are usually carried out in order to establish the
stability of the compounds and to assure the quality of the products that will be then available in the market.
In recent years we have studied a variety of pharmaceuticals of common use in our country. Among them are
antihistaminics, bronchodilators, anticonvulsives, antifungals, antibiotics, as well as mineral supplements and
excipients, both as raw materials and isolated from comercial formulations. Several new forms of these APIs
have been identified after crystallization under different conditions [1,2]. Among the compounds to be discussed
are derivatives of folic, valproic, γ-aminobutyric and gluconic acids, fluconazole, gabapentin, ciprofloxacin, and
mirtazapine. The structural characterization has been carried out by single crystal and powder diffraction
techniques using conventional laboratory X ray data and, in some instances, synchrotron radiation.
Acknowledgements. This presentation includes work carried out by G. Borges, M.C. Dávila, A. Dugarte, Y.W.
Escalante, A. Guillén, E. Hernández, R.C. López, A.G. Mora, M.A. Ramírez, J. Trejo, Dr. R.A. Toro. The
collaboration of Prof. J.M. Delgado and M.Sc. J.E. Contreras (ULA), Prof. J.A. Henao, Dr. H. Camargo and
M.Sc. J.L. Pinto (UIS, Bucaramanga, Colombia), Dr. A. Briceño, M.Sc. T. González and Dra. J. BrunoColmenárez (IVIC) and Dr. M. Pink and Dr. C-H. Chen (IUMSC, USA). Financial support comes from Grant
LAB-97000821 of FONACIT (Laboratorio Nacional de Difracción de Rayos-X) and CDCHTA-ULA Grant C1676-09-08-A.
References
1. R. Toro, J. Bruno-Colmenárez, G. Díaz de Delgado, J. M. Delgado. “Structural characterization of a new form of
clenbuterol, a well-known decongestant and bronchodilator also used as a performance-enhancing drug”. Powder
Diff. 28 (2013) 63-67.
2. R. Toro, J. Contreras, G. Díaz de Delgado, J. M. Delgado, J. L. Pinto, J. A. Henao. “Three new structural forms of
thiocolchicoside, a muscle relaxant, as shown by X-ray powder diffraction”. Powder Diff. 29 (2014) 62-68.