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Undesired drug sorption on laboratory material surfaces reduces the performance of analytical methods and results in the generation of unreliable data. Hence, we characterized the sorption of drugs and evaluated the sorption extent using a linear free energy relationship (LFER) model with Abraham solvation parameters of drugs. Furthermore, to prevent sorption, the effects of additives, such as organic solvents and salts, were evaluated.The sorption of fifteen model drugs (concentration: 2 μM), with various physicochemical properties, on materials in 0.2% dimethyl sulfoxide aqueous solutions was evaluated. Drug sorption extent on the materials was determined using high-performance liquid chromatography. The obtained results were analyzed using an LFER model with Abraham solvation parameters of the drugs. The effect of additives on the sorption of itraconazole, one of the most hydrophobic drugs among those tested in this study, was investigated.Sorption was dependent on the physicochemical properties of drugs, rather than the type of materials used, and additives altered the rate of drug sorption. Equations were developed to evaluate the sorption extent (nmol) of drugs to glass and polypropylene using the Abraham solvation parameters of the drugs.LFER modeling with Abraham solvation parameters of drugs enabled us to evaluate drug sorption on materials. All the additives altered the rate of drug sorption, and some organic solvents effectively prevented sorption. The developed LFER model would be useful for assessment of the sorption properties of compounds in in vitro evaluations in drug discovery research and various other biochemical fields.

The purpose of this study was to develop a quality evaluation method for dissolving microneedle arrays (DMNAs) and determine the spatial distribution pattern of drugs in DMNAs. Raman spectroscopy mapping was used to visualize the drug distribution in DMNAs and drug-loaded polymer films as a model. Powder X-ray diffraction (PXRD) and high-pressure liquid chromatography were also performed to characterize DMNAs. Drug-loaded polymer films and DMNAs were prepared by drying the aqueous solutions spread on the plates or casting. PXRD analysis suggested the crystallization of diclofenac sodium (DCF) in several forms depending on its amount in the sodium hyaluronate (HA)-based films. The Raman spectra of HA and DCF showed characteristic and non-overlapping peaks at 1376 and 1579 cm -1 Raman shifts, respectively. The intensity of the characteristic peak of DCF in the DCF-loaded films increased linearly with the increasing drug content in the range of 4.8 to 16.7 % (DCF, w/w). Raman imaging analysis revealed a homogenous dispersion of small DCF crystals in these films. Raman imaging indicates the distribution of DCF on the surface of the DMNA needle. This work highlights the benefit of using Raman spectroscopy mapping to reveal the spatial distribution of drugs in DMNAs.

The objective of this study was to develop a simpler and more practical quantitative evaluation method of cold flow (CF) in transdermal drug delivery systems (TDDSs). CF was forcibly induced by loading a weight on a punched-out sample (bisoprolol and tulobuterol tapes). When the extent of CF was analyzed using the area of oozed adhesive as following a previously reported method, the CF profiles were looked different between the samples 12 mm in diameter subjected to a 0.5-kg weight and samples 24 mm in diameter subjected to a 2.0-kg weight despite an equal load per unit area (4.42 g/mm2). The width of oozed adhesive around the original sample was suggested to be an index that properly describes the relationship between the load per unit area and the extent of CF. Further, it was clarified that the average CF width over the entire circumference of the sample was the same whether the samples were round or square as long as the sample area and load were the same. We also observed a linear relationship between the CF width and the aspect ratio of oval and rectangular samples. These results indicated that the CF properties of typical TDDS products lacking CF-proof processing at the edges could be determined by testing samples cut from the product rather than the whole TDDS patch. The proposed width measuring method was simple and useful for optimizing the composition of the adhesive and for testing the quality of the product.

The purpose of this study was to elucidate whether the degradation rate of insulin in lyophilized formulations is determined by matrix mobility, as reflected in glass transition temperature (Tg), or by β-relaxation, as reflected in rotating-frame spin-lattice relaxation time $${\left( {T_{{1{\text{ $ \rho $ }}}} } \right)}$$ . The storage stability of insulin lyophilized with dextran was investigated at various relative humidities (RH; 12–60%) and temperatures (40–90°C) and was compared with previously reported data for insulin lyophilized with trehalose. Insulin degradation was monitored by reverse-phase high-performance liquid chromatography. Furthermore, the $${\left( {T_{{1{\text{ $ \rho $ }}}} } \right)}$$ of the insulin carbonyl carbon in the lyophilized insulin–dextran and insulin–trehalose systems was measured at 25°C by 13C solid-state NMR, and the effect of trehalose and dextran on $${\left( {T_{{1{\text{ $ \rho $ }}}} } \right)}$$ was compared at various humidities. The degradation rate of insulin lyophilized with dextran was not significantly affected by the Tg of the matrix, even at low humidity (12% RH), in contrast to that of insulin lyophilized with trehalose. The insulin–dextran system exhibited a substantially greater degradation rate than the insulin–trehalose system at a given temperature below the Tg. The difference in degradation rate between the insulin–dextran and insulin–trehalose systems observed at 12% RH was eliminated at 43% RH. In addition, the $${\left( {T_{{1{\text{ $ \rho $ }}}} } \right)}$$ of the insulin carbonyl carbon at low humidity (12% RH) was prolonged by the addition of trehalose, but not by the addition of dextran. This difference was eliminated at 23% RH, at which point the solid remained in the glassy state. These findings suggest that the β-relaxation of insulin is inhibited by trehalose at low humidity, presumably as a result of insulin–trehalose interaction, and thus becomes a rate determinant. In contrast, dextran, whose ability to interact with insulin is thought to be less than that of trehalose, did not inhibit the β-relaxation of insulin, and thus, the chemical activational barrier (activation energy) rather than β-relaxation becomes the major rate determinant. β-Relaxation rather than matrix mobility seems to be more important in determining the stability of insulin in the glassy state in lyophilized formulations containing trehalose and dextran.