Formulation, preparation and evaluation of flunarizine-loaded lipid microspheres

Abstract

The aim of this study was to investigate the feasibility of preparing flunarizine-loaded lipid microspheres. Lipid microspheres (LMs) are excellent drug carriers for drug delivery systems (DDS) and are relatively stable and easily mass-produced. They have no particular adverse effects. LMs have been widely studied as drug carriers for water-soluble drugs, lipid-soluble drugs and inadequately soluble (in water or in lipid) drugs, in that they have a lipid layer, a water layer and an emulsifier layer. Flunarizine (FZ), a poorly water-soluble drug, was incorporated in lipid microspheres to reduce side effects by avoiding the use of supplementary agents, compared with solution injection. After investigation, the final formulation was as follows: 10% oil phase (long-chain triglyceride (LCT); medium-chain fatty acid (MCT) = 50:50); 1.2% egg lecithin; 0.2% Tween-80; 2.5% glycerin; 0.3% dl-alpha-tocopherol; 0.02% EDTA; 0.03% sodium oleate; 0.1% FZ and double-distilled water to give a total volume of 100 mL. Homogenization was the main method of preparation and the best conditions were a temperature of 40 degrees C, a pressure of 700-800 bar and a suitable cycle frequency of about 10. The particle size distribution, zeta-potential and entrapment efficacy were found to be 198.7+/-54.0 nm, -26.4 mV and 96.2%, respectively. Its concentration in the preparation was 1.0 mg mL(-1). The lipid microspheres were stable during storage at 4 degrees C, 25 degrees C and 37 degrees C for 3 months. Pharmacokinetic studies were performed in rats using a dose of 1.0 mg kg(-1). The pharmacokinetic parameters were as follows: AUC(0-t) 6.13 mug.h mL(-1), t(1/2) 5.32 h and Ke 0.16 L h(-1). The preparation data fitted a two-compartment model estimated by using 3p87 analysis software. From the observed data, FZ encapsulated in LMs did not significantly alter the pharmacokinetic characteristic compared with the FZ solution injection and did not produce a delayed release effect, when it was released in-vivo in rats. However, the availability of the drug was increased. These results suggested that this LM system is a promising option for the preparation of the liquid form of FZ for intravenous administration.

Intravenous lipid microspheres loaded with alkylated norcantharidin derivative norcantharimide: Improved stability and prolonged half‐life

“…Separately, based on the results, the absolute value of the zeta potential decreased markedly without adding 0.05% (w/v) sodium oleate. It has been reported that sodium oleate can increase the surface charge by forming an integral part of the emulsifier film, and consequently, increase the repulsion among LMs particles and help the physical stability of the formulation .…”

Intravenous bufadienolides‐loaded lipid microspheres for improving chemical stability

“…Centrifugation was carried out in a CS120GXL ultracentrifuge (HITACHI Co. Japan) at 50 000 rpm for 1.5 h. The sample temperature was preset to 4 °C. Polyallomer tubes were used and their bottoms were pricked after centrifugation with a syringe needle to collect the aqueous phase 10. The amounts of B, C, and R in the aqueous phase were estimated by HPLC and the EEs were calculated by dividing the drug concentration in the dispersed phase by that in the whole emulsion.…”

Unlocking the Potential of Oleanolic Acid: Integrating Pharmacological Insights and Advancements in Delivery Systems

“…A study was conducted to produce OA-SLN employing the film-ultrasound dispersion technique [ 108 ]. Another study aimed to produce OA-SLN using the film-ultrasonic wave dispersion technique.…”