Micronization of the drug Imiquimode with supercritical CO2 aiming to increase the solubility in physiological media and its incorporation in new release vehicles

• Grant number: 18/05237-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2018
• End date: December 31, 2022
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Angela Maria Moraes
• Grantee: Paula de Freitas Rosa Remiro
• Host Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 19/19151-5 - Evaluation of imiquimod penetration into skin and buccal mucosa before and after micronization using supercritical technology, BE.EP.PD

Abstract

Among the numerous types of Cancer, Squamous Cell Carcinoma (SCC) is one of those with higher incidence rate. The search for drugs and products to treat this Neoplasia is of high relevance, particularly considering occurrences in oral and genital mucosal tissue, to which local drug sustained delivery is still a challenge. Thus, this project aims to promote the micronization of Imiquimode drug so that it becomes more soluble in physiological media and its dispersion mucoadhesive vehicles. Aiming at the use of versatile techniques with low environmental impact, this work proposes using supercritical CO2 for the micronization process. Thus, in this project, the SAS technique (Supercritical AntiSolvent) will be used. Through this technique, the introduction of the pure liquid solvent in a column is performed until the steady-state condition is reached. Then the solution containing the solute of interest is atomized through an injector or capillary nozzle at a given rate in an anti-solvent flow. Due to the high solubility of the solvent in the anti-solvent, the precipitation of the solute (drug) occurs. Upon the micronization of the medicament, it is expected an increase in the surface area which directly influences in the solubility and in the rate of dissolution of the drug in the biological fluids will be obtained, so that the drug may be more widely employed in the treatment aiding the cure of this disease. The micronized material will be incorporated into polymeric mucoadhesive devices (films, membranes or hydrogels), aiming to broaden the range of vehicles used for their local application, usually in the form of creams and emulsions. (AU)

Scientific publications

(4)

(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)

CAMARGO, LUCAS GARCIA; ROSA REMIRO, PAULA DE FREITAS; REZENDE, GABRIELA SOUZA; SANTOS, STEPHANY DI CARLA; FRANZ-MONTAN, MICHELLE; MORAES, ANGELA MARIA. Development of bioadhesive polysaccharide-based films for topical release of the immunomodulatory agent imiquimod on oral mucosa lesions. EUROPEAN POLYMER JOURNAL, v. 151, p. 12-pg., 2021-04-16. (18/05237-2)

REMIRO, PAULA DE FREITAS ROSA; NAGAHARA, MARIANA HARUE TANIGUCHI; GHEZZI, MARTINA; FILIPPINI, ALESSIA; DEMURTAS, ANNA; PESCINA, SILVIA; SANTI, PATRIZIA; PADULA, CRISTINA; MORAES, ANGELA MARIA; NICOLI, SARA. An Alternative Device for the Topical Treatment of Oral Cancer: Development and Ex-Vivo Evaluation of Imiquimod-Loaded Polysaccharides Formulations. PHARMACEUTICS, v. 14, n. 12, p. 15-pg., 2022-12-01. (19/19151-5, 18/05237-2)

REMIRO, PAULA DE FREITAS ROSA; ROSA, PAULO DE TARSO VIEIRA; MORAES, ANGELA MARIA. Effect of process variables on imiquimod micronization using a supercritical antisolvent (SAS) precipitation technique. JOURNAL OF SUPERCRITICAL FLUIDS, v. 181, FEB 2022. (18/05237-2)

AZEVEDO, FLAVIA FIGUEIREDO; CANTARUTTI, THIAGO ANSELMO; ROSA REMIRO, PAULA DE FREITAS; BARBIERI, BEATRIZ; AZOUBEL, RAFAEL ABBOUD; TANIGUCHI NAGAHARA, MARIANA HARUE; MORAES, ANGELA MARIA; MELO LIMA, MARIA HELENA. Histological and Molecular Evidence of the Positive Performance of Glycerol-Plasticized Chitosan-Alginate Membranes on Skin Lesions of Hyperglycemic Mice. POLYMERS, v. 14, n. 21, p. 16-pg., 2022-11-01. (18/05237-2, 21/00781-9)