Hot-melt coating with Precirol ATO 5 in a fluidized-bed apparatus: Application of experimental design in the optimization of process parameters

Abstract

Hot-melt coating is a novel and cost-effective solvent-free coating technique. Commonly used excipients for hot-melt coating are lipid substances. In this work, modified fluidized-bed system was applied for coating, and additional components were used to melt and convey the excipient to the fluidized-bed apparatus. Granules containing 20% (w/w) paracetamol were coated with Precirol((R)) ATO 5 at 9.1% (w/w) coating level. The aims of this study were to define a relationship between the three process parameters (fluidization airflow, atomization air pressure and spray rate) and characteristics of the coated granules using Box-Behnken experimental design, and to identify the design space for hot-melt coating of granules with desired mechanical and drug release properties. Response surface methodology was used for data analysis and modeling. We have found that interactions between the selected input parameters have pronounced influence on coated granules size, flowability and initial drug release rate. In addition, granules size distribution is strongly influenced by fluidization airflow and atomization air pressure. Granules flowability, and total and partial areas under the drug release curve were recognized as critical quality attributes of the coated granules. Design space was determined by all three process parameters which can be referred to as critical process parameters.