Quaternary enteric solid dispersion prepared by hot-melt extrusion to mask the bitter taste and enhance drug stability

Abstract

To mask the bitterness of drug is profoundly important especially in children’s medication. This study designed and investigated a quaternary enteric solid dispersion (QESD) by secondary hot-melt-extrusion. Erythromycin (EM) was chosen as a model drug. The optimal QESD contained enteric polymer HPMCP-55, plasticizer and water-soluble polymer copovidone VA64. Raman and Atomic force microscope has exploited that majority EM was distributed in VA64 matrix, nanometer-sized EM-VA64 system was entrapped within enteric continuous phase to form a solid emulsion-like structure. For the prepared QESD, EM released concentration was far less than bitterness threshold (7 μg/mL to 20 μg/mL) in artificial saliva within the first 30 s. And dissolution rate was increased by 10% in article intestine fluid, which dominated by water-soluble VA64. Stress testing after two months at high-humidity (75% RH) and high-temperature (60 °C) revealed, compared with traditional enteric SDs, the chemical degradation of EM was slowed down in QESD. Furthermore, hydrogen and salt bonds were respectively formed between EM and VA64 and between leaking EM and HPMCP-55, which increasing the system stability and taste-masking. The effect of masking bitter taste can be satisfied as well as enhance drug dissolution rate in the intestine, and formulation physicochemical stability during storage.