Preparation of Zaleplon Microparticles Using Emulsion Solvent Diffusion Technique

Abstract

Zaleplon is a BCS class II drug suffering from poor solubility. In a trial to improve its dissolution, emulsion solvent diffusion method (ESD) was used to prepare zaleplon microparticles using sodium lauryl sulfate (SLS) as surfactant. Optimization of drug system was achieved. Particle size values of the prepared microparticles were ranged from 6.57 μm to 20.30 μm with narrow particle size distribution range. Differential scanning calorimetry (DSC) and x-ray diffraction (XRD) were used for the characterization of the prepared systems. DSC and XRD patterns showed that the zaleplon microparticles possessed decreased crystallinity. Dissolution studies demonstrated that the systemized zaleplon microparticles exhibited significantly enhanced dissolution rate when compared to pure zaleplon. A correlation could be observed between the microparticle morphology and the dissolution rate, where zaleplon microparticles that exhibited the fastest dissolution profiles had a distinctive rod shape compared to the other systems. In contrast, pure zaleplon powder appeared as irregularly-shaped particles. In conclusion, the dissolution rate of zaleplon can be enhanced to a great extent by ESD technique.

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“…This high melting point is one of the factors responsible for lower aqueous solubility. [37] This endothermic peak was not observed in the thermogram of optimized drug-loaded microparticles (F6). The broadened and shifted peaks suggest that the drug was present as molecular dispersion in the polymer matrix.…”

“…[37] Zaleplon has high melting point, which is indicative of strong crystal lattice energy. This high melting point is one of the factors responsible for lower aqueous solubility.…”

“…Zaleplon has high melting point, which is indicative of strong crystal lattice energy. [37] These characteristic peaks of the drug still existed in physical mixture and optimized batch F6 systems but with lower intensity. Whereas, the intensity of characteristic peaks of the drug was greatly minimized and broadening of peaks appear in the case of optimized batch F6, which could be attributed to the destruction of the drug crystal lattice because of progressive amorphization.…”

“…It is obvious that poorly watersoluble pharmaceuticals with lower crystallinity usually have higher dissolution rate and bioavailability. [37] Accordingly, the decrease in crystallinity of prepared Zaleplon microparticles is expected to improve its dissolution rate and bioavailability. This indicates that drug particles are dispersed at molecular level in the polymer matrices since no indication about the crystalline nature of the drugs was observed in the drugloaded microparticles.…”