Osamu Umezawa

Effect of Surface Characteristics of Theophylline Anhydrate Powder on Hygroscopic Stability

Abstract— The hygroscopicity of theophylline anhydrate has been investigated by gas adsorption and hydration kinetic methods. Type I theophylline anhydrate was obtained by recrystallization from distilled water at 95°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°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.

Effects of Tableting Pressure on Hydration Kinetics of Theophylline Anhydrate Tablets

Abstract— The effects of tableting pressure on hydration kinetics of types I and II theophylline anhydrate tablets at 95% relative humidity, 35°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).

Effect of Tableting Pressure and Geometrical Factor of Tablet on Dehydration Kinetics of Theophyline Monohydrate Tablets

AbstractThe effect of compression pressure and geometrical factors (thickness and diameter) of tablet on the dehydration kinetics of theophylline monohydrate tablets was studied using an infrared water-content measuring instrument. The dehydration rate of 2 cm diameter tablets decreased with increase in tabletting pressure. The dehydration rates of tablets also depended on tablet shape. The 2 cm diameter tablets (thin tablets) dehydrated faster than 1 cm diameter tablets (thick tablets). Dehydration of the powder bed (loosely packed tablets) and 2 cm tablets compressed at 49 MPa followed the two-dimensional phase boundary equation, and that of 2 cm diameter tablets compressed at 98 MPa and 196 MPa (thin tablets) followed the three-dimensional phase boundary equation. Dehydration of 1 cm diameter tablets compressed at 98 MPa (thick tablets) followed the one-dimensional diffusion equation. It seems that the dehydration of the tablet was controlled by the porosity and the surface area of the tablet. Therefor...