Development and Optimisation of Spironolactone Nanoparticles for Enhanced Dissolution Rates and Stability

H R Kelidari,K Morteza-Semnani,J Akbari,Mohammed Maniruzzaman,M Saeedi,H Valizadeh,Ali Farmoudeh,Ali Nokhodchi

doi:10.1208/s12249-016-0621-0

Abstract

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability.

Highlights

With the recent advent of high-throughput computational chemistry, the numbers of the poorly water-soluble or insoluble lead compounds have significantly risen
Various techniques have been reported to increase the dissolution rate of poorly water-soluble SP, such as cyclodextrin complexation approach, freeze-drying or lyophilisation, solid dispersion strategy, liposomal formulations and solid lipid nanoparticles (SLNs) approach [2,3,4,8]
Bourezg et al prepared a SP-loaded SLN formulation and reported as one of the efficient ways to enhance the dissolution of water-insoluble drugs [6]

Summary

Introduction

With the recent advent of high-throughput computational chemistry, the numbers of the poorly water-soluble or insoluble lead compounds have significantly risen. Spironolactone (SP) falls into this group due to its very low aqueous solubility and slow dissolution rate resulting in a variable and poor oral bioavailability [1,2,3,4,5,6]. Various techniques have been reported to increase the dissolution rate of poorly water-soluble SP, such as cyclodextrin complexation approach, freeze-drying or lyophilisation, solid dispersion strategy, liposomal formulations and solid lipid nanoparticles (SLNs) approach [2,3,4,8]. Lipid nanoparticles (SLN and NLC) have the capability to enhance the dissolution rate by overcoming the low and variable oral bioavailability of various poorly water-soluble drugs [4,9]. The increase in the dissolution is mainly due to a significant

Methods

Results

Conclusion