Keizo Uesugi

Evaluation of the correlation between in vivo and in vitro release of phenylpropanolamine HCl from controlled-release tablets

Abstract The dissolution behavior of two controlled-release matrix tablets, formualtions A and B, containing phenylpropanolamine HCl as a model drug was studied using a paddle method and a paddle-beads procedure. The paddle-beads method involves a system in which polystyrene beads are inserted into the dissolution medium to cause mechanical destruction or frictional force. These tablets have the advantages of pH- and agitation-independent release performance in vitro using the paddle method. These matrices and solution were orally administered to six beagle dogs, and the results were analyzed by deconvolution. In vitro dissolution curves using the paddle method did not coincide with the in vivo profiles in the fasted condition, while in vitro release using the paddle-beads method was similar to the in vivo profile in the fasted condition in dogs. The paddle-beads method may be useful for investigating in vivo/in vitro correlation of controlled-release dosage forms.

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.

Penetration of Ravuconazole, a New Triazole Antifungal, into Rat Tissues

Ravuconazole (BMS 207147, ER-30346) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. The penetration of ravuconazole into rat tissues was examined. Fifty-five 7-week-old specific pathogen free female rats were used in this study. Plasma, lung and uterus tissue of rats were taken at 1, 2, 4, 8, 12, 16, 24, 32, 48, 60, and 72 h (n = 5) after oral administration of 10 mg/kg of ravuconazole. The quantitative assays of ravuconazole by HPLC after the extraction with diethylether were conducted for each tissue sample homogenate. tmax, t 1/2, and Cmax of ravuconazole is 8 h, 16.9 h and 1.68 µg/ml, respectively. The concentrations of ravuconazole in rat uterus and lung tissues were 2–to 6 times higher than the corresponding blood concentrations. The ratio of plasma to lung levels of ravuconazole was superior to the published data of other azoles. Considering its antifungal spectrum, ravuconazole would thus be a good candidate for treatment of deep-seated fungal infections caused by Candida, Aspergillus and Cryptococcus.

Preparation of a novel type of controlled-release carrier and evaluation of drug release from the matrix tablet and its physical properties

Abstract Solved mixtures of hydrogels (SMH), composed of hydroxypropylcellulose (HPC), a pseudo-hydrogel, and ethylcellulose, a water-insoluble polymer, were prepared by solvent evaporation. Phenylpropanolamine hydrochloride was used as a model drug. The amount of drug released from a matrix tablet containing SMH powder and the drug increased with decreasing weight fraction of HPC (WFH) in SMH. SMH showed improved properties compared to HPC alone, for example, flowability and hydroscopicity. These properties increased with decreasing WFH. The sorption apparatus described in this study is capable of an immediate, sensitive and accurate response to initial moisture sorption. The kinetics of moisture sorption measurement using this apparatus is useful for a preliminary study.