Development and in vivo evaluation of an innovative “Hydrochlorothiazide-in Cyclodextrins-in Solid Lipid Nanoparticles” formulation with sustained release and enhanced oral bioavailability for potential hypertension treatment in pediatrics

Publication date: 15 April 2017 Source:International Journal of Pharmaceutics, Volume 521, Issues 1–2 Author(s): Marzia Cirri, Natascia Mennini, Francesca Maestrelli, Paola Mura, Carla Ghelardini, Lorenzo di Cesare Mannelli An innovative pediatric oral formulation of hydrochlorothiazide (HCT) (2mg/mL), endowed with improved bioavailability and sustained release properties and suitable for the hypertension treatment in pediatric patients, was developed by combining the drug-cyclodextrin complexation and the incorporation of the complex into Solid Lipid Nanoparticles (SLN). Precirol®ATO5-based SLN, with two different surfactants (Pluronic®F68 and Tween®80) loaded with the drug as such or as binary system with hydroxypropyl-beta-cyclodextrin (HPβCd) and sulfobutyl-ether-beta-cyclodextrin (SBEβCd) both as physical mixture (P.M.) or coground product (GR), were prepared using the hot high-shear homogenization followed by ultrasonication method. Loading of the drug:HPβCd both as P.M. and GR gave rise to nanoparticle formation, differently from the HCT:SBEβCd ones, with an entrapment efficiency of about 65%. Such SLN formulations showed an improvement of the drug release rate compared both to the drug suspension and to the free drug-loaded SLN. In all cases the SLN containing the GR systems exhibited better performances than the corresponding with P.M. However, the presence of Tween®80 gave rise to the complete drug release after only 150min, without providing a sus...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research