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Nickel-based superalloy Inconel 718 and austenitic stainless steel AISI 304 are joined by rotary friction welding. The changes in microstructure and mechanical properties of the dissimilar joint for solutionising, solutionising + aging, and post-weld aging treatment, with a prior solution heat treatment, are studied. Two distinct microstructural zones, the FDZ (fully deformed zone) and the TMAZ (thermo-mechanically affected zone) are observed in all weldments. The post-weld aged joint sample shows the highest tensile strength and hardness due to the precipitation of γ′ (Ni3(Ti, Al)) and γ″ (Ni3Nb) strengthening precipitates. The solution-treated sample shows the highest yield strength, while the solutionising + aging treatment is found to deteriorate the mechanical properties of the dissimilar joint. The observed changes in the mechanical properties are investigated based on microstructure and electron dispersive spectroscopy.

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The aim of this work was to develop formulations of calcitonin for pulmonary delivery to enhance the absorption and study the comparative pharmacodynamic behavior of developed formulations in rats. Formulations with different pH, absorption promoters of different classes and combination thereof at three concentration levels were prepared and instilled intratracheally in anesthetized rats. The absorption of calcitonin was measured by its hypocalcemic effect in blood collected at specific time points. The formulations having least concentration of absorption promoter with significant blood calcium reduction were selected out from three concentration levels of absorption promoters used. The relative pulmonary bioactivity of calcitonin in acetate buffer pH 6.0 and pH 3.9 was 21.0+/-1.5% and 53.9+/-2.8%, respectively, compared to subcutaneously administered calcitonin in equivalent dose. When sodium tauroglycocholate, dimethyl beta-cyclodextrin, chymostatin, and bacitracin were co-administered in acetate buffer pH 3.9 solution, the relative bioactivity of 139.1+/-7.3% was obtained. Only 72.0+/-2.7%, 79.2+/-3.9%, 83.0+/-2.1% and 87.0+/-3.9% were obtained, respectively, upon incorporation of these absorption promoters individually. It was concluded that absorption promoters in combination significantly increase the pulmonary bioactivity of calcitonin. These studies proves that calcitonin administered through the pulmonary route can yield higher systemic absorption for enhanced bioactivity.

KEYWORDS: insulin, combination of absorption promoters, blood glucose reduction, relative pulmonary bioactivity, pharmacodynamicsThe purpose of this research was to enhance the bioactivity of insulin by the pulmonary route using a combination of absorption promoters. Aliquots (100 µL) containing 1.0 IU/kg to 7.0 IU/kg doses of porcine insulin solutions with different classes of absorption promoters and combinations of these at 3 concentration levels were instilled intratracheally to the anesthetized rats. Blood concentrations of glucose were measured at specific time points. Out of 3 concentration levels of each of the absorption promoters used, the formulations having the least concentration with the maximum percentage of blood glucose reduction were selected for combining absorption promoters, and their pharmacodynamic parameters related to insulin absorption were determined. The pharmacodynamics of porcine insulin following subcutaneous administration of increasing doses were also determined. The relative pulmonary bioactivity of insulin in phosphate buffer pH 7.4 and citrate buffer pH 3.5 was 11.36% ± 1.27% and 43.20% ± 2.48%, respectively, compared to subcutaneous administration. Relative pulmonary bioactivity of 155.60% ± 5.19% was obtained when oleic acid sodium salt, sodium tauroglycocholate, bestatin, and chymostatin were coadministered in citrate buffer pH 3.5 solution. However, only 61.91% ± 3.21, 67.09% ± 3.23%, 67.24% ± 2.11%, and 69.84% ± 3.02% were obtained, respectively, upon incorporation of these absorption promoters individually. Absorption promoters in combination have significant potential for increasing the pulmonary bioactivity of insulin. These studies support the argument that pulmonary administration of insulin is a viable alternative to subcutaneous administration for diabetic patients.