A thermal/thermo-mechanical and imaging study of component distribution and interaction in pharmaceutical film coats

Meng, Jin (2012) A thermal/thermo-mechanical and imaging study of component distribution and interaction in pharmaceutical film coats. Doctoral thesis, University of East Anglia.

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Abstract

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.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Brian Watkins
Date Deposited: 15 May 2013 11:17
Last Modified: 15 May 2013 11:17
URI: https://ueaeprints.uea.ac.uk/id/eprint/42399
DOI:

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