A compatibility study of the prototype epiisopiloturine and pharmaceutical excipients aiming at the attainment of solid pharmaceutical forms

• Published in: Journal of thermal analysis and calorimetry Vol. 120; no. 1; pp. 689 - 697
• Main Authors: de Melo, Cybelly Marques, de Medeiros Vieira, Amanda Carla Quintas, da Silva do Nascimento, André Luiz, Figueirêdo, Camila Bezerra Melo, Rolim, Larissa Araújo, Soares-Sobrinho, José Lamartine, Veras, Leiz Maria Costa, de Souza de Almeida Leite, José Roberto, Neto, Pedro José Rolim, de La Roca Soares, Mônica Felts
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-04-2015; Springer
• Subjects: Analytical Chemistry; Cellulose; Chemistry; Chemistry and Materials Science; Decay; Differential scanning calorimetry; Diffraction; Excipients; Infrared spectroscopy; Inorganic Chemistry; Lactose; Measurement Science and Instrumentation; Methyl cellulose; Pharmaceuticals; Physical Chemistry; Polymer Sciences; Thermal analysis; Thermogravimetry; Thermal compatibility; Physical–chemical characterization; Epiisopiloturine
• ISSN: 1388-6150; 1588-2926; 1572-8943
• DOI: 10.1007/s10973-014-4163-y

Epiisopiloturine (EPI) is an alkaloid extracted from pilocarpine production residue that has shown promising activity for neglected illnesses like Schistosomiasis and Leishmaniasis according to in vitro studies carried out since 2009. However, its physical–chemical characteristics and its behavior in the presence of certain situations have been little explored. Since this approach provides support to the acquisition of pharmaceutical products from this molecule, this study has aimed at identifying and characterizing, through physical–chemical studies, EPI, besides evaluating its physical–chemical compatibility in the presence of excipients for solid formulations. The identification of the raw material was carried out through infrared spectroscopy. Its physical–chemical characterization was conducted using x-ray diffraction and thermal analysis thermogravimetry (TG), differential thermogravimetry, and differential scanning calorimetry (DSC) curves, besides obtaining thermal/non-isothermal decay kinetics (TNIDK). Infrared confirmed the identity of the molecule. X-ray diffraction showed crystalline behavior, with the main peak expressing at 11.1°(2
θ
). From the DSC curve and TG, its melting range was identified at 221.72–228.24 °C (∆
E
 = −148.75 J g
−1
) and its initial decay temperature at 224 °C (∆
m
 = 79.27 %), respectively, suggesting that EPI appears thermally stable. Starting from TNIDK activation energy parameters (−88.95 kJ mol
−1
), frequency factor (1.165 × 10
8
 min
−1
), and reaction order were made clear (1). Finally, in the thermal compatibility study, EPI showed to be compatible with excipients such as starch, lactose, PVP K-30, microcrystalline cellulose, and hydroxypropyl methyl cellulose. Thus, the results presented serve as support for future directed research, based on EPI, for development of solid formulations.