Development and evaluation of solid dispersion of darunavir as strategy for increase its solubility

• Grant number: 14/17954-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2015
• End date: August 31, 2016
• Field of knowledge: Health Sciences - Pharmacy - Medicines Analysis and Control
• Principal Investigator: Hérida Regina Nunes Salgado
• Grantee: Nicolle Fabri
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Protease inhibitor drugs emerged in 1994 after clarification of the mechanism of replication of human immunodeficiency virus (HIV). Studies have shown potent antiviral effect of these drugs, providing a significant improvement of the symptoms of acquired immune deficiency syndrome (AIDS), whether administered alone or in combination with inhibitors of reverse transcriptase nucleoside analogues. Darunavir is an inhibitor of dimerization and catalytic activity of the HIV protease. It selectively inhibits the cleavage of Gag-Pol polyproteins encoded in the HIV virus infected cells, thus preventing formation of mature infectious viral particles. The drug was developed in 1998, accepted by the FDA in 2006 and is imported to Brazil by Janssen-Cilag. It available as immediate release film-coated tablets containing 300, 150 and 75 mg of the drug under the name of Prezista. Darunavir composes therapy considered highly effective in the treatment of acquired immune deficiency syndrome and is one of the drugs available free of charge by the Brazilian Health System (SUS). This drug has low aqueous solubility, which presents itself as a major limiting for intestinal absorption. The low aqueous solubility drugs often leads to great variability in the bioavailability of these substances. Therefore, this study aims to provide information about (i) how the solubility and (ii) the release of darunavir from a pharmaceutical form can be modulated by use of solid dispersion applying water-soluble polymeric drug carriers. Thus, different proportions of solid dispersions and physical mixture of darunavir and water soluble polymers will be prepared by evaporation. It will be evaluated the solubility and release of drug from the dispersion and physical mixture, free and encapsulated in hard gelatin capsule. Physiologically relevant media will be used. All results will be compared with those obtained for the raw material drug. This design offers an innovative development which search engines to modulate the aqueous solubility of drugs and consequently its bioavailability.