Tetsuo Komuro

In-vitro dissolution properties of indomethacin extended-release capsules.

Abstract— In‐vitro dissolution properties of indomethacin extended‐release capsules, from samples available on the Japanese market, have been investigated using a continuous flow, column‐type dissolution apparatus and the results compared with those obtained by the paddle and the rotating basket methods. A plot of the percent of drug dissolved against the square root of time gave a straight line with the flow‐through method but not with the paddle or the rotating basket methods. The results suggest an advantage of the flow‐through method over the other two methods when extended‐release products are tested by in‐vitro dissolution.

PATHOPHYSIOLOGICAL STUDIES ON HYPERTENSION INDUCED IN RATS BU KIDNEY EXTRACT AND SALT

The renin-angiotensin-aldosterone system, electrolyte and water balance, body fluid, and neurogenic tone and reactivity of the vasculature were studied in hypertension induced in uninephrectomized rats by repeated injection of renin-rich kidney extract and 1% saline drinking. The control rats were injected with physiological saline. Various measurements were made in conscious rats on the 10th day of the treatment. As compared with the control, plasma renin concentration and serum sodium increased significantly, while plasma aldosterone and renal excretory function did not differ. Blood volume (BV) expressed as per body weight increased significantly, but absolute BV, absolute or body weight-related plasma volume and hematocrit were not significantly different. The hypotensive effect of 1-Sar-8-Ile-angiotensin II was negligible 12 hours after the preceding injection of kidney extract. It was small but significant 1 hour after the injection. Increase in water turn-over and fractional sodium excretion occurred during the development of hypertension. Spironolactone did not significantly modify the developmental course. We observed increased depressor response to hexamethonium and increased reactivities to noradrenaline and angiotensin II (A II); these response curves relatively resembled those of spontaneously hypertensive rats. Hypertensive vascular changes were seen in the kidney and heart by histology. Thus, it was suggested that a direct vascular action of A II played a partial role in this hypertensive process while aldosterone played little role. The significance of BV increase and possible contribution of A IIs other actions were discussed.