Development and Evaluation of Solid Lipid Nanoparticles of Raloxifene Hydrochloride for Enhanced Bioavailability

Abstract

Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL.

A Quality by Design Concept on Lipid Based Nanoformulation Containing Antipsychotic Drug: Screening Design and Optimization using Response Surface Methodology

“…This might be because at higher homogenization speed higher shear rate was generated lead to increase in viscosity of lipid melt which affects emulsification process. Frothing was also observed at 16000 rpm, which increased particle size [16]. Entrapment efficiency was found to be slightly lower at 8000 rpm as compared to other speeds.…”

“…As homogenization time was increased from 1 min to 10 min, the particle size was gradually decreased from 607.2 nm to 120.3 nm. With further increase to 15 min, particle size increased from 120.3 nm to 379.0 nm as longer time may cause instability for colloidal particles due to high input of energy that leads to aggregation of colloidal particles into larger particles [16,17]. Entrapment efficiency was slightly lower in case of 1 min homogenization.…”

Encapsulation challenges, the substantial issue in solid lipid nanoparticles characterization

“…In the mentioned study, the drug‐loaded SLNs were centrifuged using a high‐speed refrigerated centrifuge to separate the supernatant through Nanosep centrifuge tubes. Then, the amount of drug in the supernatant was determined by a UV–Vis spectrophotometer . EE was ranged from 55% to 66% in the study by Kushwaha et al However, considering the poor solubility of the drug in water, possibility of the entrance of unloaded drug into the supernatant was low; therefore, free unloaded drug crystals might have remained on the filter of Falcon tube.…”

Antibiotic-Resistant Bacteria: Prevalence in Food and Inactivation by Food-Compatible Compounds and Plant Extracts

“…The isolated compound was shown to have antibacterial and antibiofilm activities against clinical isolates of Stenotrophomonas maltophilia, including a resistant strain. 96 It could therefore be developed as a safe antibiotic alternative or for use in combination.…”