Pharmaceutical applications of micro-thermal analysis

Micro-thermal analysis is a recently introduced thermoanalytical technique that combines the principles of scanning probe microscopy with thermal analysis via replacement of the probe tip with a thermistor. This allows samples to be spatially scanned in terms of both topography and thermal conductivity, whereby placing the probe on a specific region of a sample and heating, it is possible to perform localized thermal analysis experiments on those regions. In this minireview, the principles of the technique are outlined and the current uses within the polymer sciences described. Current pharmaceutical applications are then discussed; these include the identification of components in compressed tablets, the characterization of drug-loaded polylactic acid microspheres, the analysis of tablet coats, and the identification of amorphous and crystalline regions in semicrystalline samples. The current strengths and weaknesses of the technique are outlined, along with a discussion of the future directions in which the approach may be taken

BSA-loaded solid lipid microparticles prepared by spray congealing and spray freeze drying.

The aim of this research was to explore the possibility of using two different production technologies, such as Spray Congealing (SC) and Spray Freeze Drying (SFD) in the preparation of Solid Lipid Microparticles (SLMs) containing proteins. Bovine Serum Albumin (BSA) was employed as model protein due to its well-known physical-chemical state characterization. SC technology is based on spraying a fluid consisting of a solution or suspension of active pharmaceutical ingredient in a molten carrier, which melts at a relatively low temperature (50-80\ub0C). Conversely, in SFD process, a solution or a biphasic system containing the dissolved protein is sprayed into a cryogenic liquid (-70\ub0C) to form droplets which freeze upon the contact with the cryogenic solution and this suspension is then freeze dried to obtain a fine powder. In the first case BSA might be denaturated by heat, while in latter case, the degrading action could result from both the use of solvents and the freeze-drying process. Six batches of microparticles employing three lipid (Precirol\uaeATO 5, Dynasan\uae114 and Dynasan\uae118) with different melting temperatures and containing 10% and 20 % of BSA were produced by SC. On the contrary, using SFD technology , two formulations containing 9% and 16% of BSA in the presence of Dynasan\uae114 as lipid carrier, lecithin and poloxamer 407 as surfactants and sucrose as lyoprotector were preparedt. The results showed process yields ranging between 65% to 80% and encapsulation efficiencies above 90% and between 80% and 90% for SC and SFD formulations, respectively. SEM analysis displayed that all batches produced by SC were spherical and not aggregated with a mean volume diameter ranging between 150-300 micron. Conversely, SFD formulations showed numerous surface fractures, which appeared or as small cracks or as noticeable lacks of lipid membrane. Physical-chemical characterization using differential scanning calorimetry (DSC), UV spectrophotometry in fourth derivative mode and Raman microspectroscopy was performed. Thermal analysis showed that the protein degradation in solid state started around 80\ub0C. UV spectrophotometry, however, highlighted that no spectral variations occurred between aqueous solution of BSA (reference) and BSA solutions obtained by hot extraction (70-75\ub0C) of the SLMs produced by both techniques. The Raman microspectroscopy, associated with the curve fitting analysis of amide I band, which represents the characteristic band of the alfa-helical structure, between 1600 and 1720 cm-1 confirmed, finally, the structural stability of BSA loaded into SLMs produced by SC. In the case of SLMs prepared by SFD, this spectroscopic technique highlighted BSA structural changes which were not revealed by the other two techniques. The modifications of the secondary structure of the BSA seemed to be due to the greater number of damaging events that affected the protein, such as the denaturant action of the solvent and the aggregation phenomenon at the solid-vapour interface during freeze-drying. In conclusion, the results showed that the Spray Freeze Drying caused a structural alteration of the protein, while the Spray Congealing technology allowed to produce microparticles without denaturing the BSA secondary structure

Volumetric properties and enthalpies of solution of alcohols CkH2k+1OH (k=1,2,6) in 1-methyl-3-n-alkylimidazolium bis-(trifluoromethylsulfonyl)amide (n=2,4,6,8,10).

International audienc

Recent application of the spray congealing technology: production of microparticles loaded with phytochemicals or protein

Since more than ten years our group has been actively involved in research on spray congealing, one of the useful methods for the preparation of solid lipid microparticles. Till now this technology has been successfully employed for producing microspheres loaded with numerous conventional small molecular weight drugs, but its application to phytochemicals or proteins has been rarely reported. This research aimed to evaluate the suitability of spray congealing for the production of delivery systems loaded with phytochemicals or proteins. Gelucire 50/13 microparticles loaded with sylimarin (a low water soluble Sylibum marianum extract) both pure or in a activated status (mechanochemical activation with croscarmelose sodium) were prepared and characterised (particle size, morphology, drug loading, solubility, solubilization kinetics, DSC, FT-IR and XRD analysis). The results showed that spherical microspheres having encapsulation efficienty > 90% and a significant improvement of sylimarin solubilization kinetic were obtained. The in vivo absorbtion studies on rats showed remarkable enhancement of the oral bioavailability of the sylimarin-activated loaded systems compared to commercial product.Recently the suitability of spray congealing for the microencapsulation of a model protein (bovine serum albumin, BSA) using lipid carriers (Precirol ATO 5, Dynasan 114 and 118) has also been evaluated. Preliminary results suggested that the technique enabled the production of BSA loaded systems without affecting the BSA stabilit