Hidenobu Ando

Determination of the mechanical impact force in the in vitro dissolution test and evaluation of the correlation between in vivo and in vitro release

Abstract The mechanical impact force in the paddle-beads method was determined. A manometric catheter was passed into the dissolution vessel through a hole, and the mechanical impact force was measured. In the present study, this mechanical force was evaluated as an impulse. The impulse increased with increasing number of beads added in the medium; in particular, the impulse increased markedly with more than 2500 beads in 250 ml dissolution medium. A close relationship was observed between the drug release rate and impulse. The profile of in vitro release using the paddle-beads method with rotation at 25 rpm in 250 ml of medium containing 2500 beads was similar to that of in vivo release in the fasted condition in dogs.

Effect of moisture on crystallization of theophylline in tablets

AbstractNeedle-like crystals appeared on the surface of theophylline tablets containing anhydrous theophylline, hygroscopic materials such as potassium, and other formulation ingredients, when stored under conditions of high relative humidity. X-ray powder diffraction studies on these crystals showed that anhydrous theophylline was converted to the hydrate.Crystal growth was accelerated by increased moisture uptake in tablets containing the hygroscopic materials polyethylene glycol 6000 or sodium chloride. The appearance of needle-like crystals on the surface of tablets resulted in a decrease in the rate of release of theophylline.

Water behavior during drug release from a matrix as observed using differential scanning calorimetry

Abstract A solid made from a dissolved mixture of hydroxypropylcellulose and ethylcellulose (SMH) was used as a controlled-release filler, and phenylpropanolamine hydrochloride (PPA) was used as a model drug. With increases in weight fraction of hydroxypropylcellulose (WFH) in the matrix, drug release and water penetration into the matrix decreased Water behavior daring drug release from a SMH matrix was studied by using differential scanning calorimetry (DSC). During the initial stage of dissolution, the water penetrating into the matrix acted as non-freezing water. As the water content of the matrix increased and freezable water was detected at levels that were related to drug release. It was also presumed that before hydrating the whole matrix, water penetrated into the dry portion of the matrix and hydrated the polymer, while further penetrating water did not increase the water content of the hydrated portion, but newly hydrated a dry portion of the matrix.

Further Observation of Content Uniformity of d-α-Tocopheryl Acetate as an Oily Drug in Granules Obtained by Wet Granulation with a High-Shear Mixer

Using d-α-tocopheryl acetate (VE) as a model drug, we investigated the effects of the amount of binder solution on content uniformity of oily drugs in granules obtained by wet granulation with a high-shear mixer. When the amount of binder solution was below the water volume for the plastic limit, the content of VE was less than 50% in the fractionated fine granules, but was more than 200% in the fractionated large granules. Large variations were seen in the contents of VE even if the granulation time was extended up to 30 min. This large variation was not decreased by the milling process. On the other hand, when the amount of binder solution was at or above the water volume for the plastic limit, less variation was observed in the content of VE throughout the granules, and the content of VE was fairly uniform. Nuclei rich in VE were formed when VE was adsorbed with the powder before granulation. When the amount of binder solution was below the water volume for the plastic limit, the shearing force of mixer blades to the granules was low, so that the nuclei rich in VE were not fragmented. This led to the nonuniformity of VE content throughout the granules. On the other hand, when amount of binder solution was at or above the water volume for the plastic limit, the shearing force of mixer blades against the granules increased and became sufficient to fragment the nuclei. This led to the uniformity of VE content throughout the granules. This study showed that content uniformity of VE in the granules can be achieved by controlling the physical shearing force of mixer blades by regulating the amount of binder solution.

Effect of Crystallization of Theophylline on Physical Properties of Tablets

AbstractTablets containing anhydrous theophylline, a hygroscopic material such as magnesium chloride or potassium acetate, and other constituents were stored for 4 and 12 weeks under 90% relative humidity at 37°C. During storage, whisker-like crystals appeared on the surface of the tablets. The crystals were observed under a scanning electron microscope. Changes were found in the physical properties of these tablets: crushing strength, friability, disintegration time and dissolution rate.