Bioavalability of furosemide complexed with beta cyclodextrin: in vitro - in vivo correlation evaluation from human volunteers

• Grant number: 10/03133-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2011
• End date: July 31, 2013
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Cristina Helena dos Reis Serra
• Grantee: Cristina Helena dos Reis Serra
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Bioavailability studies evaluate the presence of the drug in the body from the administration of a pharmaceutical form over time. The in vitro-in vivo correlation relates to the establishment of a rational relationship between the biological properties, or parameters derived from those produced by a pharmaceutical form and its properties or physicochemical characteristics. The establishment of such a correlation of data can enable the replacement of in vivo studies for the demonstration of bioequivalence studies in vitro, in the case of changes in the manufacturing process after the product registration. Additionally, these studies are used in applications for biowaiver, or exemption from the testing of pharmaceutical bioequivalence. To obtain a in vitro - in vivo correlation, several factors must be considered. Initially, it is important that the limiting step of drug absorption is the process of dissolution. Moreover, it can expect a in vitro - in vivo correlation for drugs belonging to Class II of the biopharmaceutical classification, and systems for controlled release of drugs, since that in these two cases, the limiting step of the process of absorption of the drug is the dissolution (Amidon et al., 1995). For the in vitro - in vivo correlation test, it is required three formulations containing the drug of interest, which have different profiles of extended release. The systems feature matrix material as the main example of controlling the release of polymeric substances trainers hydrophilic matrices (Aceves et.al., 2000). The furosemide is a drug that presents questions in the class definition given by the biopharmaceutical classification system. According to World Health Organization (WHO), the drug is classified as Class II and IV, with problems mainly on the determination of parameters of permeability (WHO, 2006). However, these problems can be overcome, as shown in work published by Kaukonen et al (2007), where the group furosemide in a complex matrix of thermally carbonized porous silicon and the results, the group concluded that there were improvements in both the solubility as the permeability of the drug. Based on these observations, attempts to establish the in vitro - in vivo correlation from complex of furosemide - cyclodextrin developed by Spricigo et al(2008), since results were significantly better with respect to the physicochemical properties, solubility and dissolution of furosemide when the drug is complexed with cyclodextrin. (AU)