Development of a Carvedilol Oral Liquid Formulation for Paediatric Use
Blanca Chiclana-Rodríguez,
Encarnacion Garcia-Montoya,
Khadija Rouaz-El Hajoui,
Miquel Romero-Obon,
Anna Nardi-Ricart,
Marc Suñé-Pou,
Josep M. Suñé-Negre,
Pilar Pérez-Lozano
Affiliations
Blanca Chiclana-Rodríguez
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
Encarnacion Garcia-Montoya
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
Khadija Rouaz-El Hajoui
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
Miquel Romero-Obon
Quality Assurance Pharmaceutical Sites Director—Laboratorios ALMIRALL, Ctra. de Martorell, 41-61, 08740 Sant Andreu de la Barca, Spain
Anna Nardi-Ricart
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
Marc Suñé-Pou
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
Josep M. Suñé-Negre
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
Pilar Pérez-Lozano
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
Carvedilol (CARV) is an ‘off-label’ β-blocker drug to treat cardiovascular diseases in children. Since CARV is nearly insoluble in water, only CARV solid forms are commercialized. Usually, CARV tablets are manipulated to prepare an extemporaneous liquid formulation for children in hospitals. We studied CARV to improve its aqueous solubility and develop an oral solution. In this study, we assessed the solubility and preliminary stability of CARV in different pH media. Using malic acid as a solubility enhancer had satisfactory results. We studied the chemical, physical, and microbiological stability of 1 mg/mL CARV–malic acid solution. A design of experiment (DoE) was used to optimize the CARV solution’s preparation parameters. A 1 mg/mL CARV solution containing malic acid was stable for up to 12 months at 25 °C and 30 °C and 6 months at 40 °C. An equation associating malic acid with CARV concentrations was obtained using DoE. Microbiological data showed that the use of methylparaben was not necessary for this period of time. We successfully developed an aqueous CARV solution suitable for paediatrics and proven to be stable over a 12-month period.