A thermal/thermo-mechanical and imaging study of component distribution and interaction in pharmaceutical film coats
Ethyl cellulose (EC) is one of the most important coating materials for controlled release formulations. To achieve the desirable drug release, the physical properties of EC films incorporated with various functional additives need to be fully understood. Therefore, the aim of this project is to characterize the physical properties of EC films incorporated with various plasticizers and pore forming agents, hence to understand the drug release mechanisms in relation to the physical characteristics of EC films. The thermal properties of EC powder and EC films were initially characterized by means of thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), modulated temperature DSC (MTDSC) and dynamic mechanical analysis (DMA). Subsequently, oleic acid (OA), dibutyl sebacate (DBS) and medium chain triglycerides (MCT) were incorporated as plasticizers while hydroxypropyl methylcellulose (HPMC) was utilized as the pore forming agent. The thermal, thermo-mechanical and phase distribution of EC films incorporated with plasticizers and/or HPMC were investigated using MTDSC, DMA and localized thermal analysis (LTA). These results were compared with the thermal properties and scanning electron microscopy (SEM) images of the free films after immersion into water, pH 1.2 and 6.8 buffers. Dissolution of metoprolol succinate and paracetamol from SureSpheres® pellets coated by these films were then carried out. OA and DBS were more efficient than MCT for EC films. OA and DBS showed good compatibility with EC, whereas at 20% plasticizer level and beyond, EC/MCT films presented two EC phases with 8% and 24% MCT respectively. The addition of HPMC to EC films did not show a significant effect on their thermal properties. However, the phase distribution of HPMC domains was affected by the HPMC levels. After immersion into the release media, HPMC generated water filled pores quickly in the first two hours. The shape and sizes of these pores were corresponding to the phase distribution of HPMC domains. The release from these films appeared to follow zero-order kinetics, except for metoprolol succinate from pellets coated by EC/plasticizer/HPMC films, which followed the Higuchi model. It is suggested that the dissolution rate of HPMC, film properties and solubility of the model drugs is the ratedetermining step.
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