CO2 utilization as a gas antisolvent in the production of glibenclamide nanoparticles, glibenclamide-HPMC, and glibenclamide-PVP composites

Abstract

Glibenclamide is an antidiabetic drug that also acts as an anti-inflammatory factor and reduces oxidative stress, medullary edema, and heart attack. Glibenclamide has high permeability and poor solubility in water (BCS class II). This work addresses particle size reduction of Glibenclamide using the gas antisolvent (GAS) to improve the drug dissolution rate. Three process parameters were studied at three levels: pressure (120, 140, and 160 bar), temperature (308, 318, and 328 K), and initial solute concentration (15, 45, and 75 mg/mL). The Box-Behnken design method was applied to optimize the process conditions. The coprecipitation of Glibenclamide with polyvinyl pyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) was investigated by GAS at optimum pressure and temperature conditions (i.e., 160 bar and 308 K). Furthermore, the particles produced were characterized by high performance liquid chromatography, powder x-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectrometry, dynamic light scattering, and field emission scanning electron microscopy. The maximum dissolution rate in water obtained after 75 minutes was 36.6 %, 88.3 %, 94.1 %, and 97.7 % for unprocessed Glibenclamide, Glibenclamide nanoparticles, Glibenclamide-HPMC and Glibenclamide-PVP composites, respectively. Glibenclamide-HPMC nanocomposites produced by GAS showed the smallest particle size, while Glibenclamide-HPMC exhibited the fastest dissolution rate.

Keywords

• Glibenclamide
• Gas antisolvent
• HPMC
• PVP
• Dissolution rate