Yoshiteru Takahashi

An application of water-in-oil and gelatin-microsphere-in-oil emulsions to specific delivery of anticancer agent into stomach lymphatics.

The efficiency of water-in-oil (W/O) and gelatin-microsphere-in-oil (W/O-G) emulsions as drug delivery systems for achieving specificity into lymphatics was evaluated in the rat stomach. Following injection into the stomach wall, radioactivities of131I-labeled o-iodohippuric acid (IH, watersoluble model compound) and [14C]tripalmitin (TP, tracer of oil) in blood, regional lymph nodes, thoracic lymph, and stomach were determined. Since increased transfer of TP indicated the facilitation of lymphatic transport of IH following injection of W/O and W/O-G emulsions, the existence of a special transport mechanism through which drug and oil are delivered together was confirmed for this injection site. W/O and W/O-G emulsions increased the concentration-time curve (AUC) of IH in the regional lymph nodes (1.7 and 5.5 times that of aqueous solution injection, respectively), so the improvement of bioavailability was accomplished. In addition, a prolonged release of IH and decrease of its maximum blood concentration were obtained following injection of W/O-G emulsion. These results suggest that W/O and W/O-G emulsions satisfy many of the criteria of an ideal drug delivery system for cancer chemotherapy. An abundant supply of lymphatic vessels in the stomach wall exhibited the efficiency of these delivery systems more clearly than did thigh muscle.

Polymorphism of Fostedil: Chracterization and Polymophic Change by Mechanical Treatments

AbstractTwo crystal forms of fostedil were characterized using X-ray diffraction patterns and infrared spectra. The melting points of polymorph I and II were 95.3 °C and 96.4 °C, respectively.Solubility studies demonstrated that, of the two fostedil polymorphs, form II was slightly more soluble than form I. The free energy difference between two polymorphs was small (71.8 cal/mol at 37 °C). Both crystals melted at about 60 °C in water considerably below the melting points.Compression of form II at a compression force of 500 - 1000 kg/cm2 induced polymorphic changes in the crystal. Similar changes also were produced through grinding. The effects of some diluents on the polymorphic transformation from form II into form I by grinding were also studied. Microcrystalline cellulose and corn starch showed a polymorphic transfomation-accelerating effects.Form I is more suitable for the pharmaceutical preparation.

PREPARATION AND SCALE-UP STUDY OF TREATED FAMOTIDINE FOR THE DEVELOPMENT OF ORALLY DISINTEGRATING TABLETS USING A COMPLEX FLUIDIZED-BED GRANULATOR EQUIPPED WITH A PARTICLE-SIZING MECHANISM

Objective: Bitter taste-masked drug substance should be needed for the development of orally disintegrating tablets (ODT). We selected a new type of a complex fluidized-bed granulator equipped with a particle-sizing mechanism for treating famotidine (FAM). This study was conducted to demonstrate the critical process parameter, which controls particle size of treated FAM, to determine its acceptable particle size considering uniformity of assay and to perform scale-up study from a laboratory scale to a commercial scale. Methods: Particle size of treated FAM was evaluated by changing spraying air pressure on the operation of a complex fluidized-bed granulator. Uniformity of assay in granules after blending and tablets were compared at different particle size of treated FAM. On the scale-up study, particle size and assay of treated FAM in both scales were evaluated. Results: The particle size of treated FAM decreased as the increase in spraying air pressure in relation to the spraying mist size. Better uniformity of assay was observed when the diameter of treated FAM was 20 µm compared to that of 50 µm. Therefore, target particle size of treated FAM was set at approximately 20 µm. Similar qualities could be obtained between both scales in the points of particle size and assay. Conclusion: On the operation of a complex fluidized-bed granulator, spraying air pressure was the critical process parameter that controlled particle size of treated FAM. On Scale-up study of treated FAM, spraying air pressure in relation to the spraying mist size was important.