The Influence of the Polymer Type on the Quality of Newly Developed Oral Immediate-Release Tablets Containing Amiodarone Solid Dispersions Obtained by Hot-Melt Extrusion.

Abstract

The present study aims to demonstrate the influence of the polymer-carrier type and proportion on the quality performance of newly developed oral immediate-release tablets containing amiodarone solid dispersions obtained by hot-melt extrusion. Twelve solid dispersions including amiodarone and different polymers (PEG 1500, PEG 4000; PEG 8000, Soluplus®, and Kolliphor® 188) were developed and prepared by hot-melt extrusion using a horizontal extruder realized by the authors in their own laboratory. Only eleven of the dispersions presented suitable physical characteristics and they were used as active ingredients in eleven tablet formulations that contain the same amounts of the same excipients, varying only in solid dispersion type. The solid dispersions’ properties were established by optical microscopy with reflected light, volumetric controls and particle size evaluation. In order to prove that the complex powders have appropriate physical characteristics for the direct compression process, they were subjected to different analyses regarding their flowability and compressibility behavior. Additionally, the Fourier transform infrared spectroscopy and X-ray diffraction analysis were performed on the obtained solid dispersions. After confirming the proper physical attributes for all blends, they were processed into the form of tablets by direct compression technology. The manufactured tablets were evaluated for pharmacotechnical (dimensions–diameter and thickness, mass uniformity, hardness and friability) and in vitro biopharmaceutical (disintegration time and drug release) performances. Furthermore, the influence of the polymer matrix on their quality was determined. The high differences in flow and compression performances of the solid dispersions prove the relevant influence of the polymer type and their concentration-dependent plasticizing properties. The increase in flowability and compressibility characteristics of the solid dispersions could be noticed after combining them with direct compression excipients owning superior mechanical qualities. The influence of the polymer type is best detected in the disintegration test, where the obtained values are quite different between the studied formulations. The use of PEG 1500 alone or combined in various proportions with Soluplus® leads to rapid disintegration. In contrast, the mixture of PEG 4000 and Poloxamer 188 in equal proportions determined the increase in disintegration time to 120 s. The use of Poloxamer 188 alone and a 3:1 combination of PEG 4000 and Soluplus® also generates a prolonged disintegration time for the tablets.