Effects of formulation variables and characterization of guaifenesin wax microspheres for controlled release.

Sustained-release wax microspheres of guaifenesin, a highly water-soluble drug, were prepared by the hydrophobic congealable disperse method using a salting-out procedure. The effects of formulation variables on the loading efficiency, particle properties, and in-vitro drug release from the microspheres were determined. The type of dispersant, the amount of wetting agent, and initial stirring time used affected the loading efficiency, while the volume of external phase and emulsification speed affected the particle size of the microspheres to a greater extent. The crystal properties of the drug in the wax matrix and the morphology of the microspheres were studied by differential scanning calorimetry (DSC), powder x-ray diffraction (XRD), and scanning electron microscopy (SEM). The DSC thermograms of the microspheres showed that the drug lost its crystallinity during the microencapsulation process, which was further confirmed by the XRD data. The electron micrographs of the drug-loaded microspheres showed well-formed spherical particles with a rough exterior.

Microencapsulation of a hydrophilic drug into a hydrophobic matrix using a salting-out procedure. II. Effects of adsorbents on microsphere properties.

Wax microspheres of the hydrophilic drug guaifenesin were prepared by the congealable disperse-phase method using a salting-out procedure. In order to improve the particle properties of the microspheres, adsorbents (colloidal silica, magnesium stearate, and talc) were used during preparation. The effects of adsorbents on microsphere properties such as the angle of repose (AR), compressibility index (CI), geometric mean diameter (GMD), loading efficiency (LE), and in vitro drug release (DR) were determined. The AR, CI, and GMD of the microspheres were significantly reduced in the presence of the adsorbents. Increase in the concentrations of colloidal silica and magnesium stearate led to lower LE and faster DR, while talc showed no effect, which could be due to the particle diameter and specific surface area of the adsorbents. The microspheres prepared with colloidal silica were chosen to be compressed into tablets since they were smaller, more uniform, and had better flow properties than those made with magnesium stearate and talc. The in vitro drug release profile of the microsphere tablets was compared with that of commercially available Mucinex, sustained release guaifenesin matrix tablets. Similar release profiles were observed between the two tablets. Scanning electronic microscopy (SEM) studies of the broken tablets revealed that the deformation of the microspheres caused by compression was minimal.

Solubility of guaifenesin in the presence of common pharmaceutical additives.

The aqueous solubility of guaifenesin, a highly water-soluble drug, in the presence of salts, sugars, and cosolvents was determined at 25 degrees C and 40 degrees C. The solubility of drug at both temperatures was reduced with increasing concentrations of salts and sugars. The extent of reduction in drug solubility was dependent on the type of salts and sugars used. The salting-out coefficient of additives was calculated by plotting log-linear solubility profiles of the drug against the concentrations of the additives. The solubility of guaifenesin, a neutral compound, was found to be higher at lower pH values, which could be due to hydrogen-bonding effects. At 25 degrees C, glycerin, PEG 300, and propylene glycol increased the solubility of drug at low solvent concentrations while the solubility was reduced at high concentrations. At 40 degrees C, the solubility of drug was reduced at all concentrations of cosolvents. The thermodynamic events accompanying the solubility process were discussed to explain the solubility phenomena observed in the presence of additives. The reduced aqueous solubility of guaifenesin in the presence of additives greatly improved the entrapment of drug into controlled-release wax microspheres.