title: Self-Nanoemulsified Drug Delivery System of Hydrochlorothiazide for Increasing Dissolution Rate and Diuretic Activity.
abstract: Hydrochlorothiazide (HCTZ) is a class IV drug according to the Biopharmaceutical Classification System. This study aimed the development of self-nanoemulsifying drug delivery system (SNEDDS) for HCTZ as an approach to overcome the biopharmaceutical limitations. Pre-formulation screening and ternary phase diagrams were carried out to select the oil phase, the surfactant, and the co-surfactant as the amount of each constituent. The optimized formulations, with reduced amount of surfactant, and composed of medium chain triglycerides, Cremophor EL and Transcutol P did not affect the pH or show drug incompatibilities. The SNEDDS were stabilized by the nanoscale globules and high negative zeta potential. All the physicochemical characterization assays were performed in biorelevant media to better predict the in vivo performance. The enhanced dissolution rate of the SNEDDS reflected in the in vivo diuretic activity, presenting a natriuresis, kaliuresis, and chloriuresis at early stages and an increased volume of total urine compared with HCTZ alone. The designed SNEDDS produced an improvement in the pharmacodynamics due to high dissolution and probable inhibition of intestinal efflux protein by Cremophor EL. The use of SNEDDS demonstrated to be an efficient approach to modulate the absorption of HCTZ and drug therapeutics.
authors.affiliation: Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Universidade Federal de Santa Catarina, J/K 207, 88040-900, Florianópolis, SC, Brazil. cassi_ana@yahoo.com.br.
authors.forename: Cassiana
authors.initials: C
authors.lastname: Mendes
authors.affiliation: Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Universidade Federal de Santa Catarina, J/K 207, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Buttchevitz
authors.affiliation: Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Universidade Federal de Santa Catarina, J/K 207, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Jéssica Henriques
authors.initials: JH
authors.lastname: Kruger
authors.affiliation: Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Universidade Federal de Santa Catarina, J/K 207, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Caon
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: de Oliveira Benedet
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Elenara
authors.initials: E
authors.lastname: Lemos-Senna
authors.affiliation: Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Universidade Federal de Santa Catarina, J/K 207, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Marcos Antônio Segatto
authors.initials: MAS
authors.lastname: Silva
mesh_terms: D004232:Diuretics / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000494:pharmacology; D012995:Solubility
chemical_list: D004232:Diuretics; D004655:Emulsions; D006852:Hydrochlorothiazide; C000515:cremophor EL; D005990:Glycerol
keywords: biorelevant media; diuretic activity; hydrochlorothiazide; self-nanoemulsifying drug delivery system