Biomedical subjects

O Umezawa

Publications and source records attributed to O Umezawa.

10 recordsLinked to original sources

PubMed1992

Effect of geometric factors on hydration kinetics of theophylline anhydrate tablets.

The effect of tablet thickness on the hydration kinetics of types I and II theophylline anhydrate tablets at 95% relative humidity and 35 degrees C was studied with various kinetic equations. Samples of 1- and 2-cm-diameter tablets (1 g) were compressed at 1000 kg/cm2. Types I and II tablets expanded by 11-17% in volume during hydration to the monohydrate. The thickness expansion of all tablets exceeded the diameter expansion. After the hygroscopicity test, the final expansion ratio of type I tablets was more than that of type II tablets. The hydration kinetics analysis suggested that the hydration of theophylline anhydrate tablets proceeds as follows: Hydration of the 1-cm-diameter type I tablet followed the two-dimensional phase boundary equation, and that of the 1-cm-diameter type II tablet followed the three-dimensional phase boundary equation, but those of the 2-cm-diameter types I and II tablets followed the equation for two-dimensional growth of nuclei. The hydration kinetics of tablets does not depend on the nature of bulk powder but on geometrical factors (tablet thickness and porosity).

Chemical Phenomena↗

PubMed1991

Effects of tableting pressure on hydration kinetics of theophylline anhydrate tablets.

The effects of tableting pressure on hydration kinetics of types I and II theophylline anhydrate tablets at 95% relative humidity, 35 degrees C, have been studied by using various kinetic equations. Relations between tablet expansion and hydration were studied. Samples of 2 cm diameter tablets (1 g) were compressed at 5, 10 and 20 MPa. The hydration of types I and II tablets decreased with increased tableting pressure. The time required for 50% hydration of 2 cm diameter tablets, compressed at various pressures suggests that the tablet hydration rate was affected by the tableting pressure. Types I and II tablets expanded 11.37-16.75% in volume during hydration to the monohydrate. The thickness expansion of the tablets exceeded the diameter expansion as the tablet structure was not uniform owing to the orientation of particles during the compression. The final expansion ratio of the tablets increased with increased tableting compression pressure. The Hancock Sharp constant (m) and fitting of the kinetic data to a suitable model suggested that the hydration of theophylline anhydrate tablets followed the two-dimensional phase boundary equation (type I tablets) or the three-dimensional phase boundary equation (type II tablets).

Chemical Phenomena↗

PubMed1990

Effect of surface characteristics of theophylline anhydrate powder on hygroscopic stability.

The hygroscopicity of theophylline anhydrate has been investigated by gas adsorption and hydration kinetic methods. Type 1 theophylline anhydrate was obtained by recystallization from distilled water at 95 degrees C, and type II was obtained by dehydration of theophylline monohydrate. The X-ray diffraction pattern of types I and II agreed with the data of theophylline anhydrate. However, the diffraction peaks of the (200) and (400) planes of type I were much stronger than those of type II. The particles of type I were clear crystalline-like single crystals. However, the particles of type II had many cracks. The gas affinity balance (H/N) of type II, measured by gas adsorption, was about 7 times that of type I. After the hygroscopicity of types I and II had been tested at various levels of relative humidity (RH) at 35 degrees C, type I was stable at less than 82% RH, but transformed into the monohydrate at more than 88% RH. Type II was stable at less than 66% RH and transformed into the monohydrate at less than 75% RH. The hydration data of type I at 88% RH and type II at 75% RH were calculated for hydration kinetics using various solid-state kinetic models, but no particular model could be preferred from these data.

Adsorption↗

PubMed1987

Pharmacokinetic study of carbamazepine and its epoxide metabolite in humans.

A major metabolite of carbamazepine (CBZ), CBZ-10, 11-epoxide (EPO), has been reported to possess anticonvulsant properties. Therefore, the present study was undertaken in order to develop a pharmacokinetic model to predict the behavior of EPO in the body after administration of CBZ. The serum concentration-time curves after oral administration of solution of CBZ (200 mg) or EPO (150 mg) in six healthy subjects showed the characteristic "nose", suggesting that disposition of CBZ or EPO could be described by the two-compartment model. The kinetic parameters of disposition for CBZ and EPO were calculated by the method of Wagner, assuming the absolute bioavailabilities of CBZ and EPO to be 1.0 and 0.81, respectively. Total body clearance and elimination rate constant of EPO were very much larger than those of the parent drug but there was no statistically significant difference in the distribution volume between CBZ and EPO. The formation rate of EPO was calculated by a deconvolution method, and obeyed Michaelis-Menten kinetics. Based on these findings, a pharmacokinetic model of the fate of CBZ and EPO in humans was developed and the time courses of CBZ and EPO in serum after oral administration of three tablet preparations and a solution containing 200 mg of CBZ were simultaneously fitted to this model by solving the differential equations by the Runge-Kutta-Gill method. There was good agreement between calculated and observed serum values, suggesting that the present model is appropriate to describe the formation and disposition of EPO from CBZ. The formation rate constant of EPO (Vmax/Km/V1) was approximately one-fifteenth of the elimination rate constant of EPO. This suggested a flip-flop model in which the formation of EPO was rate-limiting in humans. The observation that the serum concentrations of EPO after administration of CBZ were one-tenth to one-twentieth of those of the parent drug was well explained by the flip-flop kinetics of EPO, together with the large differences in total body clearance and elimination rate constant between CBZ and EPO.

Adult↗

PubMed1987