Preparation and evaluation of solid dispersions of piroxicam and Eudragit S100 by spherical crystallization technique

Abstract

Objective: To improve the dissolution rate of piroxicam (PX), enteric-release microparticles having solid dispersion (SD) structure were prepared in one step. Methods: SD of PX and Eudragit S100 (Eu S100) with the aid of silicon dioxide (Aerosil® 200), as an antiadhesion agent, were prepared by spherical crystallization technique. The microparticles were characterized by differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy and were evaluated for yield, encapsulation efficiency, flowability, packability, and drug release (at pH 1.2 and pH 7.4). The samples were stored at severe condition [40°C, 75% relative humidity (RH)] for 3 months to investigate their stability. The effects of the polymer–drug and polymer–Aerosil ratios on the characteristics of the microparticles were also investigated. Results: PX microparticles exhibited significantly improved micromeritic properties in comparison to the crystalline pure drug. The dissolution of drug from microparticles in phosphate buffer (pH 7.4) indicated a significant increase in dissolution of PX when dispersed in Eu S100. The results of X-ray powder diffraction and differential scanning calorimetry analysis indicated that in microparticles at 2:1 Eu S100:PX ratio the crystalline form of PX was disordered, suggesting that PX was highly dispersed in microparticles, as that in the amorphous state. Fourier transform infrared spectroscopy analysis demonstrated the presence of intermolecular hydrogen bonding between PX and Eu S100 in SD. In stability test, the release profiles of the microparticles were unchanged as compared with the freshly prepared SDs; amorphous PX in the SD particles did not crystallize under storing at 40°C, 75% RH for 3 months.

Keywords:

• Aerosil
• enteric microparticles
• Eudragit S100
• piroxicam
• spherical crystallization