A study of phase separation in peptide-loaded HPMC films using Tzero-modulated temperature DSC, atomic force microscopy, and scanning electron microscopy

Hussain, Samana, Grandy, David B., Reading, Mike and Craig, Duncan (2004) A study of phase separation in peptide-loaded HPMC films using Tzero-modulated temperature DSC, atomic force microscopy, and scanning electron microscopy. Journal of Pharmaceutical Sciences, 93 (7). pp. 1672-1681. ISSN 0022-3549

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Abstract

Despite the widespread use of drug-loaded polymeric systems, there is still considerable uncertainty with regard to the nature of the distribution of the drug within the polymer matrix. The aim of this investigation was to develop thermal and microscopic techniques whereby the miscibility and spatial distribution of a model peptide, cyclosporin A (CyA), in hydroxypropyl methylcellulose (HPMC) films may be studied. The new technique of Tzero-modulated temperature differential scanning calorimetry (Tzero MTDSC), scanning electron microscopy (SEM), and pulse force mode atomic force microscopy (PFM-AFM) were used in conjunction to study films prepared using a solvent evaporation process, with a solvent extraction study performed to elucidate the nature of the observed phases. Tzero MTDSC studies showed glass transitions for both the HPMC and CycA, with the Tg for the HPMC and CycA seen for the mixed systems. SEM showed two spherical phases of differing electron density. PFM-AFM also showed spheres of differing adhesion that increased in size on addition of drug. Pixel intensity analysis indicated that the smaller spheres corresponded to CycA. Exposure of the films to dichloromethane, in which CycA is soluble but HPMC is not, resulted in the presence of voids that corresponded well to the spheres suggested to correspond to the drug. It was concluded that the system had undergone extensive or complete phase separation, and that the thermal and microscopic techniques outlined above are an effective means by which this issue may be studied.

Item Type: Article
Uncontrolled Keywords: hydroxypropyl methylcellulose,polymer films,cyclosporin a,phase separation,sem,mtdsc,pulse force afm
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: Rachel Smith
Date Deposited: 08 Mar 2011 16:15
Last Modified: 17 Jan 2024 01:23
URI: https://ueaeprints.uea.ac.uk/id/eprint/25782
DOI: 10.1002/jps.20066

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