Experimental design applied to forced degradation of Nitazoxanide and Sofosbuvir pharmaceutical drugs

• Grant number: 17/13095-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2017
• Effective date (End): July 18, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal researcher: Renato Lajarim Carneiro
• Grantee: Benedito Roberto de Alvarenga Junior
• Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 19/22048-1 - Evaluation of the degradation products of Ritonavir antiretroviral drug during hot extrusion process (HME), BE.EP.DR

Abstract

Safety and efficacy of a drug are extremely important factors. These parameters are determined, for example, by dosage forms and impurities. Degradation products are impurities and it must be studied in order to ensure the stability of drugs and to develop of analytical techniques to detect such impurities. Regulatory agencies make general recommendations for study forced degradation, once specific recommendations would be difficult to implement due to great difference in stability and chemical properties of the different active pharmaceutical ingredients. Therefore, multivariate methodology arises as an alternative in the studies of forced degradation, allowing a more realistic simulation of the storage conditions of the drug. In addition, this methodology simulates systems where the analyte is exposed to degradation conditions have not been yet studied in the literature, opening the possibility for identification of new degradation products. In light of the foregoing, the present work aims to use the multivariate methodology with the application of design of experiment concepts in the forced degradation study of two drugs: Nitazoxanide (NTZ, used for a great range of parasites), and Sofosbuvir (SFR, used against HCV virus causative agent of Hepatitis C). The modified central composite design will be used to evaluate the variables temperature, pH, concentration of oxidizing agent (H2O2) and radiation with UV light in the degradation of NTZ and SFR. The response monitored by HPLC-UV and HPLC-MS will be statistically evaluated to understand the influence and relationship between the variables, in order to predict the optimal conditions to the product stability and also to possible synthesis of degradation products. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, CECILIA C. P.; DAYO OWOYEMI, BOLAJI C.; ALVARENGA-JR, BENEDITO R.; ALVAREZ, NATALIA; ELLENA, JAVIER; CARNEIRO, RENATO L.. Synthesis and solid-state characterization of diclofenac imidazolium monohydrate: an imidazolium pharmaceutical ionic liquid. CrystEngComm, v. 22, n. 32, p. 5345-5354, AUG 28 2020. (17/13095-0, 10/16520-5)

ARDILA, JORGE ARMANDO; DE ALVARENGA JUNIOR, BENEDITO ROBERTO; DURANGO, LUIS CUADRADO; FELIPE SOARES, FREDERICO LUIS; PERLATTI, BRUNO; CARDOSO, JOSIANE DE OLIVEIRA; OLIVEIRA, REGINA VINCENZI; FORIM, MOACIR ROSSI; CARNEIRO, RENATO LAJARIM. Design of experiments applied to stress testing of pharmaceutical products: A case study of Albendazole. European Journal of Pharmaceutical Sciences, v. 165, OCT 1 2021. (17/13095-0, 10/16520-5)

ALVARENGA, JR., BENEDITO ROBERTO; NERES XAVIER, FELIPE AUGUSTO; FELIPE SOARES, FREDERICO LUIS; CARNEIRO, RENATO LAJARIM. Thermal Stability Assessment of Vegetable Oils by Raman Spectroscopy and Chemometrics. FOOD ANALYTICAL METHODS, v. 11, n. 7, SI, p. 1969-1976, JUL 2018. (17/13095-0, 10/16520-5)

DE ALVARENGA JUNIOR, BENEDITO ROBERTO; CARNEIRO, RENATO LAJARIM. Chemometrics Approaches in Forced Degradation Studies of Pharmaceutical Drugs. Molecules, v. 24, n. 20, OCT 2019. (17/13095-0)

CARNEIRO, RENATO L.; DE MELO, CRISTIANE C.; DE ALVARENGA JR, BENEDITO R.; OWOYEMI, BOLAJI C. DAYO; ELLENA, JAVIER; DA SILVA, CECILIA C. P.. Mechanochemical synthesis and characterization of a novel AAs-Flucytosine drug-drug cocrystal: A versatile model system for green approaches. Journal of Molecular Structure, v. 1251, MAR 5 2022. (10/16520-5, 17/13095-0)

DE ALVARENGA, JR., BENEDITO ROBERTO; MOSESON, DANA E.; CARNEIRO, RENATO LAJARIM; TAYLOR, LYNNE S.. Impact of Polymer Type on Thermal Degradation of Amorphous Solid Dispersions Containing Ritonavir. MOLECULAR PHARMACEUTICS, DEC 2021. (19/22048-1, 17/13095-0)