Irbesartan desmotropes: Solid-state characterization, thermodynamic study and dissolution properties

• Published in: Journal of pharmaceutical analysis Vol. 9; no. 5; pp. 339 - 346
• Main Authors: Araya-Sibaja, Andrea Mariela, Maduro de Campos, Carlos Eduardo, Fandaruff, Cinira, Vega-Baudrit, José Roberto, Guillén-Girón, Teodolito, Navarro-Hoyos, Mirtha, Cuffini, Silvia Lucía
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01-10-2019; Xi'an Jiaotong University, Journal of Pharmaceutical Analysis; Escuela de Química, Universidad de Costa Rica, San Pedro de Montes de Oca, 2060, San José, Costa Rica%Programa de Pós-Gradua??o em Física, Universidade Federal de Santa Catarina, Florianópolis, Brazil%Independent Researcher, 06472-005, Barueri, S?o Paulo, Brazil%Laboratorio Nacional de Nanotecnología LANOTEC-CeNAT-CONARE, 1174-1200, Pavas, San José, Costa Rica; Laboratorio de Investigación y Tecnología de Polímeros POLIUNA, Escuela de Química, Universidad Nacional de Costa Rica, Heredia, 86-3000, Costa Rica%Escuela de Ciencia e Ingeniería de los Materiales, Tecnológico de Costa Rica, Cartago, 159-7050, Costa Rica%Escuela de Química, Universidad de Costa Rica, San Pedro de Montes de Oca, 2060, San José, Costa Rica%Instituto de Ciência e Técnica, Universidade Federal de S?o Paulo, S?o José dos Campos, S?o Paulo, Brazil; Escuela de Ciencia e Ingeniería de los Materiales, Tecnológico de Costa Rica, Cartago, 159-7050, Costa Rica; Laboratorio Nacional de Nanotecnología LANOTEC-CeNAT-CONARE, 1174-1200, Pavas, San José, Costa Rica; Xi'an Jiaotong University; Elsevier
• Subjects: Antihypertensives; Bioavailability; Desmotropic forms; Differential scanning calorimetry; Dissolution; Feasibility studies; Fourier transforms; Intrinsic dissolution rate; Irbesartan; Microscopy; Pharmaceutical industry; Phase transitions; Raman spectroscopy; Raw materials; Relative humidity; Scanning electron microscopy; Solid-state characterization; Tautomerism; X-ray diffraction; Tautomerism; Solid-state characterization; Irbesartan; Desmotropic forms; Intrinsic dissolution rate
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2019.07.001

Irbesartan (IBS) is a tetrazole derivative and antihypertensive drug that has two interconvertible structures, 1H- and 2H-tautomers. The difference between them lies in the protonation of the tetrazole ring. In the solid-state, both tautomers can be isolated as crystal forms A (1H-tautomer) and B (2H-tautomer). Studies have reported that IBS is a polymorphic system and its forms A and B are related monotropically. These reports indicate form B as the most stable and less soluble form. Therefore, the goal of this contribution is to demonstrate through a complete solid-state characterization, thermodynamic study and dissolution properties that the IBS forms are desmotropes that are not related monotropically. However, the intention is also to call attention to the importance of conducting strict chemical and in solid-state quality controls on the IBS raw materials. Hence, powder X-ray diffraction (PXRD) and Raman spectroscopy (RS) at ambient and non-ambient conditions, differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM) techniques were applied. Furthermore, intrinsic dissolution rate (IDR) and structural stability studies at 98% relative humidity (RH), 25 °C and 40 °C were conducted as well. The results show that in fact, form A is approximately four-fold more soluble than form B. In addition, both IBS forms are stable at ambient conditions. Nevertheless, structural and/or chemical instability was observed in form B at 40 °C and 98% RH. IBS has been confirmed as a desmotropic system rather than a polymorphic one. Consequently, forms A and B are not related monotropically.
•Valuable solid-state characterization data of irbesartan, data which were formerly absent from the literature, are presented herein.•It has been demonstrated that irbesartan solid forms are not polymorphs; they are desmotropes. Therefore, they are not related monotropically as was previously reported in the literature.•These results address the concerns of dealing with tautomerism as a minor phenomenon and the classification of desmotropes as polymorphs.•The importance of strict quality control analysis of pharmaceutical raw materials, not only chemical but also in the solid-state, is evidenced in the case of irbesartan.