Design, characterization and in vivo evaluation of nanostructured lipid carriers (NLC) as a new drug delivery system for hydrochlorothiazide oral administration in pediatric therapy

Marzia Cirri,Lavinia Maestrini,Francesca Maestrelli,Natascia Mennini,Paola Mura,Carla Ghelardini,Lorenzo Di Cesare Mannelli

doi:10.1080/10717544.2018.1529209

Marzia Cirri, Lavinia Maestrini + Show 5 more

Open Access

https://doi.org/10.1080/10717544.2018.1529209

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Journal: Drug Delivery	Publication Date: Jan 1, 2018
Citations: 85	License type: open-access

Affiliation: University of Florence, Menarini Group (Italy)

Abstract

The hydrochlorothiazide (HCT) low solubility and permeability give rise to limited and variable bioavailability; its low stability makes it difficult to develop stable aqueous liquid formulations; its low dose makes the achievement of a homogeneous drug distribution very difficult. Thus, the aim of this study was to investigate the effectiveness of a strategy based on the development of nanostructured lipid carriers (NLC) as an innovative oral pediatric formulation of HCT with improved therapeutic efficacy. The performance of various synthetic and natural liquid lipids was examined and two different preparation methods were employed, i.e. homogenization-ultrasonication (HU) and microemulsion (ME), in order to evaluate their influence on the NLC properties in terms of size, polydispersity index, ζ-potential, entrapment efficiency, gastric stability, and drug release properties. Precirol®ATO5 was used as solid lipid and Tween®80 and Pluronic®F68 as surfactants, formerly selected in a previous study focused on the development of HCT-solid lipid nanoparticles (SLNs). The presence of Pluronic®F68 did not allow ME formation. On the contrary, using Tween®80, the ME method enabled a higher entrapment efficiency than the HU. Regardless of the preparation method, NLCs exhibited great entrapment efficiency values clearly higher than previous SLNs. Moreover, NLC-ME formulations provided a prolonged release, which lasted for 6 h. In particular, NLC-ME containing Tween®20 as Co-Surfactant showed the best performances, giving rise to a complete drug release, never achieved with previous SLN formulations, despite their successful results. In vivo studies on rats confirmed these results, displaying their best diuretic profile. Moreover, all HCT-loaded NLC formulations showed higher stability than the corresponding SLNs.

Highlights

IntroductionThe lack of suitable specific pediatric formulations often leads to the use of extemporaneous preparations obtained starting from the dosage form for adults, by dilution of liquid formulations, opening or capsules or finely grinding of tablets, administered as suspensions
Children are a special category of patients
We considered it worthy of interest to investigate the usefulness of employing nanostructured lipid carriers (NLC) as a new carrier for the oral administration of HCT in pediatric therapy, in order to assess their actual advantages compared to solid lipid nanoparticles (SLNs), in terms of drug entrapment efficiency, gastric and storage stabilities and drug release properties

Summary

Introduction

The lack of suitable specific pediatric formulations often leads to the use of extemporaneous preparations obtained starting from the dosage form for adults, by dilution of liquid formulations, opening or capsules or finely grinding of tablets, administered as suspensions. Such manipulations give rise to a series of disadvantages, including in particular minor dosing accuracy, unknown and variable bioavailability, poor compliance for both children and caregivers, and lack of data about the preparation stability (Pandolfini & Bonati, 2005; Standing & Tuleu, 2005). Stability problems of HCT in aqueous solution have been reported (Mollica et al, 1971)

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