Cellulose acetate phthalate-chitosan based nanoparticles for transdermal delivery of captopril in pediatric patients

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The Pediatric Committee at the European Medicines Agency identified the needs of the development of age-appropriate formulation of captopril in pediatric population for the treatment of cardiovascular diseases and diabetic nephropathy. Captopril (CAT) is currently administered by extemporaneous liquid formulation or tablet due to its limited water stability. Therefore, polymeric nanoparticles were developed for transdermal delivery of CAT for obtaining a prolonged CAT release as well as an easy dosage control with high compliance of pediatric patients. Cellulose acetate phthalate (CAP) and chitosan (CH) were chosen to prepare nanoparticles by nanoprecipitation method-dropping technique without using surfactants. CAP nanoparticles and CAP nanoparticles combined with CH in different concentrations (1:1 w/w and 1:3 w/w) were produced both unloaded and loaded with CAT. Nanoparticles were characterized in terms of size, drug loading efficiency and physical stability during the time (1-28 days). Chemical stability of drug in the dispersion was investigated. Results show that CAP nanoparticles have no drug loading capacity, whereas CH allows the encapsulation of CAT; highest drug loading is obtained when 1:3 CAP:CH w/w ratio was used (64.6±7.6%). The particle preparation at 60°C enhances the interaction of CAT with the polymer matrix. The size of loaded CAP nanoparticles is 515.6±5.2 nm, whereas that of CAP-CH nanoparticles is 279.8±2.5 nm (1:1 w/w ratio) and 408.1±9.5 nm (1:1 w/w ratio) with a PDI values around 0.2, resulting in a homogeneous system. Good physical stability of all formulations during the time is observed. At the moment, CAT appears stable in the dispersions. In conclusion, CAP-CH nanoparticles prepared using a 1:3 w/w ratio show good properties for developing suitable formulation for transdermal delivery of CAT.