An investigation into the surface deposition of progesterone on poly (d,l-) lactic acid microspheres using micro-thermal analysis.

Abstract

Polylactic acid microspheres are well established as delivery vehicles for a range of low molecular weight and proteinaceous drugs (1–3). However, there is arguably a paucity of information available regarding the physical characteristics of these spheres, with few studies (4) addressing the issue of the manner in which drugs are distributed through the polymeric matrix. Following earlier studies (5,6) we recently investigated the use of modulated temperature DSC (MTDSC) as a means of monitoring the distribution of progesterone within poly(d,l-lactide) spheres using a range of loadings up to 50% w/w (7). By monitoring the thermal response of the spheres we obtained strong evidence for the drug being present as a separate amorphous phase at 30% w/w loading and as a distinct crystalline phase at 50% w/w loading. Complementary SEM studies showed marked changes in the surface morphology of the spheres at these two concentrations, leading to the suggestion of surface drug deposition. However, it was not possible at that stage to definitively establish the location of the drug using the methodologies available. A recent advance within the thermal analysis field has been the introduction of micro-thermal analysis (micro-TA, 8–10). This method is based on the same principles as conventional AFM but involves the replacement of the probe tip with a Wollaston wire loop. The apex of the wire is etched away to leave the silver filament exposed, resulting in a higher resistance in this section of the tip. Application of a voltage therefore results in Joule heating, hence one may apply a thermal signal to highly specific regions of a sample. In addition, the technique allows isothermal measurement of thermal conductivity by rastering over the surface and measuring the tip resistance. The technique has attracted considerable interest, particularly within the polymer science field, as it represents a unique method of performing thermal analysis on highly specific regions of a sample without the necessity of heating the material in its entirety. Early studies on pharmaceutical materials have also yielded highly encouraging results (11,12). The ability of micro-TA to perform localised thermal analysis suggests that the method may be a means of establishing whether the progesterone is indeed present on the surface of the aforementioned microspheres. The objective of the present study was therefore to investigate the use of micro-TA as a novel means of characterising the surface of the PLA microspheres, with a particular view to obtaining further evidence for the presence or absence of progesterone on the exterior of the spheres.