Solid lipid nanoparticles and nanosuspension of adefovir dipivoxil for bioavailability improvement: formulation, characterization, pharmacokinetic and biodistribution studies

Abstract

The present study was aimed at developing colloidal formulations like solid lipid nanoparticles (SLN) and nanosuspension (NS) for improving bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor which displays poor oral bioavailability. SLNs were prepared by solvent injection method while NS was prepared by pearl milling method. The prepared formulations were characterized for physicochemical parameters such as particle size, ζ potential, drug content, X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC). Pharmacokinetic and biodistribution studies were performed in mice to evaluate in vivo fate of the formulations. The SLNs showed particle size of 267 ± 18 nm and entrapment efficiency of 73.5 ± 2.12%. The particle size obtained for NS was 393 ± 13 nm against 710 ± 70 μm for bulk drug, which led to significant improvement in saturation solubility. DSC and XRD studies of NS and SLN showed reduction in crystallinity while in vitro studies showed improved dissolution rate in both cases. Pharmacokinetics studies of orally administered formulations in mice exhibited higher plasma concentration compared to plain drug. Biodistribution studies showed higher accumulation of drug in liver, kidneys, intestine and stomach. The higher concentration of AD in liver after 24 hr highlights its potential advantage for effective treatment of chronic hepatitis infection. The relative bioavailability for adefovir NS and SLN were 52.46% and 78.23% respectively compared to 34.34% bioavailability obtained after administration of adefovir micro suspension (AMS), indicating suitability of both nanoparticulate formulations for improving bioavailability. SLNs were found to performed better as compared to NS for improving the bioavailability of AD.

Study on Formulation, in vivo Exposure, and Passive Targeting of Intravenous Itraconazole Nanosuspensions

“…Slow dissolution rate is one of the key issues affecting the clinical application of newly developed medicines that are poorly soluble in water, and reducing particle size has been one of the often adopted strategies to conquer the problem. The micronization of poorly soluble drugs, where particles are reduced to the micrometer range, improves dissolution rate because of the associated increase of surface area without actually increasing the solubility of the drug (Teeranachaideekul et al., 2008; Chavhan, 2013). However, when the particle size is decreased to the nanometer range, through formulation technologies, such as nanoemulsion (Bu et al., 2014; Yadav et al., 2016; Kaur et al., 2017), liposome (Koshkina et al., 2004), solid lipid nanoparticle (Baek and Cho, 2015), micelle (He et al., 2016; Chen et al., 2017), and nanosuspension (Ghosh et al., 2008; Maged et al., 2016; Yin et al., 2016), both the surface area and the solubility of the drugs are increased significantly, resulting in substantially increased dissolution rate.…”

Development and Evaluation of a Reconstitutable Dry Suspension Containing Isoniazid for Flexible Pediatric Dosing

“…A generally acceptable PDI value of 0.37 ± 0.04 was recorded for the RDS powder, indicating that the particles were mostly homogenous and well dispersed within the formulation. The measured ZP was −41.10 ± 5.57 mV, showing a stable system, where a ZP value of ±30 mV is considered a stable and satisfactory formulation [24,29]. Representative graphs based on an independent measurement of the zeta potential and particle size distribution are shown in Figure 1a,b.…”

Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery and the Effects of Preparation Parameters of Solvent Injection Method

“…SLNs had a PS of 267 ± 18 nm and an EE of 73.5 ± 2.12%. In rats, the relative bioavailability of adefovir-loaded SLNs was 78.23%, higher than those values of nanosuspension (52.46%) and micro-suspension (34.34%) after oral administration [ 149 ].…”