Multidrug co-crystals of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Proton Pump Inhibitors (PPIs): development, characterization and biological evaluation in vitro and in vivo

• Grant number: 18/23357-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2020
• End date: September 07, 2023
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Marlus Chorilli
• Grantee: André Luiz Carneiro Soares do Nascimento
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach, AP.TEM
• Associated scholarship(s): 21/08289-6 - Novel drug-drug solid-forms of NSAIDs and PPIs: development, characterization and biological evaluation in vitro and in vivo, BE.EP.PD

Abstract

The development of an Active Pharmaceutical Ingredient (API) is divided into several stages and lasts an average of twelve years. It was estimated that only 0.005% of the new molecules with therapeutic activity come to be tested in humans, and for commercialization this factor decreases drastically. Therefore, the search for new modifications involving APIs that are already in the market, such as obtaining co-crystals, becomes so important, once that the modification of physicochemical properties are strategies that bring benefits that go beyond the increase in bioavailability, and have a relatively low cost. The co-crystals have gained a great interest of the pharmaceutical industry due to their improvements in the solubility, as well as in the reduction of the tendencies to undergo phase transformations. The clinical success of some API-API therapeutic hybrids, as in the case of celoxib-tramadol, has left multidrug co-crystals in the worldwide emphasis. This approach may confer greater pharmacological and pharmacotechnical performance, resulting in potential advantages due to additive and/or synergistic effects. According to the Biopharmaceutical Classification System (BCS), Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are class II drugs, which have low aqueous solubility and act by inhibiting the Cyclooxygenase enzymes (COX) responsible for mediating inflammatory processes. However, in therapy with non-selective NSAIDs, these drugs also inhibit normal processes of homeostasis and therefore cause a number of side effects, causing abdominal discomfort, nausea, and other gastrointestinal symptoms. Proton Pump Inhibitors (PPIs), such as omeprazole, have an extremely short serum half-life (1-2 hours), acting to reduce gastric acid production by inhibiting the H+/K+ ATPase enzyme found in the parietal cells of the stomach and have been the basis of therapy in several disorders related to the gastrointestinal tract. In this scenario, this research project intends to develop, characterize and evaluate biologically, using in vitro and in vivo assays, multidrug co-crystals (API-API) of non-selective NSAIDs and PPIs. In addition to factors related to intellectual property, these co-crystals will bring with them numerous advantages over isolated drugs, allowing the formation of thermodynamically stable APIs. The pharmacological properties of both are expected to be maintained where this new therapeutic entity may minimize the gastrointestinal symptoms caused by NSAID therapy. (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)

MARENA, GABRIEL DAVI; DOS SANTOS RAMOS, MATHEUS APARECIDO; CARVALHO, GABRIELA CORREA; DE LIMA, LAURA CAMINITTI; CARNEIRO SOARES DO NASCIMENTO, ANDRE LUIZ; SABIO, RAFAEL MIGUEL; RODERO, CAMILA FERNANDA; SPOSITO, LARISSA; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Development and characterization of an amphotericin B - loaded nanoemulsion applied to Candida auris biofilms control. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 74, p. 14-pg., 2022-07-20. (19/26821-7, 18/25377-3, 19/09597-6, 19/09831-9, 18/23442-2, 14/50928-2, 17/22758-3, 18/23357-5)

RICCIO, BRUNO VINCENZO FIOD; DO NASCIMENTO, ANDRE LUIZ CARNEIRO SOARES; MENEGUIN, ANDREIA BAGLIOTTI; RODERO, CAMILA FERNANDA; SANTOS, KAIO PINI; SABIO, RAFAEL MIGUEL; DE ANNUNZIO, SARAH RAQUEL; FONTANA, CARLA RAQUEL; BARUD, HERNANE DA SILVA; FERRARI, PRISCILEILA COLERATO; et al. Solid Dispersions Incorporated into PVP Films for the Controlled Release of Trans-Resveratrol: Development, Physicochemical and In Vitro Characterizations and In Vivo Cutaneous Anti-Inflammatory Evaluation. PHARMACEUTICS, v. 14, n. 6, p. 21-pg., 2022-06-01. (19/19817-3, 18/09088-1, 18/23015-7, 18/25377-3, 18/23357-5, 19/00164-0)

NASCIMENTO, A. L. C. S.; FERNANDES, R. P.; CARVALHO, A. C. S.; FRIGIERI, I.; ALVES, R. C.; CHORILLI, M.. Insights for Alzheimer?s disease pharmacotherapy and current clinical trials. NEUROCHEMISTRY INTERNATIONAL, v. 159, p. 13-pg., 2022-07-31. (18/23357-5)

NASCIMENTO, ANDRE L. C. S.; FERNANDES, RICHARD P.; CHARPENTIER, MAXIME D.; TER HORST, JOOP H.; CAIRES, FLAVIO J.; CHORILLI, MARLUS. Co-crystals of non-steroidal anti-inflammatory drugs (NSAIDs): Insight toward formation, methods, and drug enhancement. PARTICUOLOGY, v. 58, p. 227-241, OCT 2021. (13/09022-7, 18/23357-5, 18/24378-6)