Dynamic calibration for the in-line NIR monitoring of film thickness of pharmaceutical tablets processed in a fluid-bed coater.

NIR spectroscopy has been extensively employed for the in-line monitoring of pharmaceutical processes as one of the key PAT implementation tools. Nevertheless, pharmaceutical processes such as fluid-bed coating have not fully made the most of the NIR in-line monitoring primarily due to a difficulty in handling random in-line spectra. In this study, novel approaches to develop a reasonable dynamic calibration model were proposed; averaging and clustering. Pharmaceutical test tablets were coated with HPMC-based materials using a fluid-bed processor. During the 160 min coating process under tangential spraying mode, 10 tablets were sampled out at every 10 min mark for actual coating thickness measurements. NIR spectra at and near each 10 min mark were treated and processed by the averaging and clustering operations. Averaging of 21 spectra resulted in a reasonably good dynamic calibration model whose determination coefficient was estimated as high as 0.9916. The PCA-based clustering turned out to be substantially helpful especially when a large number of NIR spectra were averaged. A prediction experiment verified that our dynamic calibration model can control the coating thickness in-line as good as 3% deviated from the actual thickness, which can offer a reasonable end-point for the fluid-bed coating process.

Freezing point depression of water in phospholipid membranes: a solid-state NMR study.

Lipid-water interaction plays an important role in the properties of lipid bilayers, cryoprotectants, and membrane-associated peptides and proteins. The temperature at which water bound to lipid bilayers freezes is lower than that of free water. Here, we report a solid-state NMR investigation on the freezing point depression of water in phospholipid bilayers in the presence and absence of cholesterol. Deuterium NMR spectra at different temperatures ranging from -75 to + 10 degrees C were obtained from fully (2)H2O-hydrated POPC (1-palmitoyl-2-oleoylphosphatidylcholine) multilamellar vesicles (MLVs), prepared with and without cholesterol, to determine the freezing temperature of water and the effect of cholesterol on the freezing temperature of water in POPC bilayers. Our 2H NMR experiments reveal the motional behavior of unfrozen water molecules in POPC bilayers even at temperatures significantly below 0 degrees C and show that the presence of cholesterol further lowered the freezing temperature of water in POPC bilayers. These results suggest that in the presence of cholesterol the fluidity and dynamics of lipid bilayers can be retained even at very low temperatures as exist in the liquid crystalline phase of the lipid. Therefore, bilayer samples prepared with a cryoprotectant like cholesterol should enable the performance of multidimensional solid-state NMR experiments to investigate the structure, dynamics, and topology of membrane proteins at a very low temperature with enhanced sample stability and possibly a better sensitivity. Phosphorus-31 NMR data suggest that lipid bilayers can be aligned at low temperatures, while 15N NMR experiments demonstrate that such aligned samples can be used to enhance the signal-to-noise ratio of is 15N chemical shift spectra of a 37-residue human antimicrobial peptide, LL-37.