Microencapsulation of a hydrophilic drug into a hydrophobic matrix using a salting-out procedure and development of tableted microspheres
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The hydrophobic congealable disperse phase method for preparing microspheres of hydrophilic drugs has often resulted in low loading efficiency (< 20%) as the drugs partition into the external water phase during emulsification. One way to improve the loading efficiency using this procedure is to reduce drug solubility in the external phase using salting-out agents. In order to identify suitable salting-out agents, the aqueous solubility of guaifenesin in the presence of salts, sugars and co-solvents was determined. Based on the results obtained, a novel process using wetting agents in the disperse phase and a saturated salt solution as the external phase was developed to improve drug loading. Loading efficiency was significantly improved and values up to 86.3% were obtained. The key variables drug/wax ratio and the types of salts and wetting agents, were further optimized for drug entrapment and dissolution rate using a full 33 factorial design experiment. The effects of other formulation variables on microsphere properties were also determined. The crystal properties of the drug in the wax matrix and the morphology of the microspheres were studied by differential scanning calorimetry (DSC), x-ray diffraction (XRD) and scanning electron microscopy (SEM). The thermograms for the microsphere samples showed that the drug lost its crystallinity on melting and resolidification, which was further confirmed by the XRD and SEM data. In order to improve the particle properties of the microspheres, inert adsorbents (colloidal silica, magnesium stearate and talc) were used. The geometric mean diameter, angle of repose and compressibility index of the microspheres were significantly reduced in the presence of adsorbents. The microspheres prepared using colloidal silica were formulated into tablets. The tablets were compared with those for commercially available Mucinex®, sustained release guaifenesin matrix tablets. The results indicated that dissolution profiles obtained were similar for both types of tablets.