Biomedical subjects

Takahiro Uchida

Publications and source records attributed to Takahiro Uchida.

21 records · Page 2Linked to original sources

PubMed2002

Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutine.

The objectives of this study were to produce acid soluble, polyvinylacetal diethylaminoacetate (AEA) microspheres containing trimebutine (as maleate), using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, to characterize their in-vitro release properties, and to evaluate the taste-masking potential of this formulation in human volunteers. The pH of the external aqueous phase was the critical factor in achieving a high loading efficiency for trimebutine in the microencapsulation process; nearly 90% (w/w) loading efficiency was obtained at above pH 10. Trimebutine was completely released from AEA microspheres within 10 min in a dissolution test at pH 1.2, simulating conditions in the stomach, whereas at pH 6.8, the pH in the mouth, only small quantities of trimebutine were released in the initial 1-2 min. The results of a gustatory sensation test in healthy volunteers confirmed the taste-masking effects of the AEA microspheres. Finally, an attempt was made to encapsulate the salts of other basic drugs (lidocaine, imipramine, desipramine, amitriptyline, promethazine and chlorpheniramine) into AEA microspheres using the w/o/w emulsion evaporation method. The loading efficiencies were ranked in almost inverse proportion with the solubility of the drugs in the external aqueous phase. This study demonstrated the possibility of masking the taste of salts of basic drugs by microencapsulation with AEA using a w/o/w emulsion solvent evaporation method.

Algorithms↗

PubMed2002

Evaluation of myopathy risk for HMG-CoA reductase inhibitors by urethane infusion method.

Purpose of the present study was to evaluate the myopathy risk using a urethane infusion method following oral administration of five kinds of commercial HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (HCRIs), (pravastatin (PV), simvastatin (SV), cerivastatin (CeV), atorvastatin (AV), and fluvastatin (FV)) alone or with coadministration of bezafibrate (BF). The solubility of HCRIs in various solvents was determined as a criterion of the physicochemical property. The plasma creatine phosphokinase (CPK) level as a marker of myopathy in normal rats was screened under urethane infusion after oral administration of HCRI alone or with BF coadministration. Also, renal tissue specimens were prepared and the myoglobin remaining in the tissue was visualized by the labeled avidin-biotin technique. The plasma CPK level in normal rats under urethane infusion following oral administration of five kinds of HCRI increased as the dose of HCRI increased, and coadministration of BF further increased the CPK level for each drug. The risk of myopathy evaluated from the CPK level was ranked as follows: CeV>FV>AV>SV>PV. Myoglobin deposition was observed in the cast of proximal tubules, cytoplasm of distal tubules and collecting ducts of rat kidney extracted from rats treated with HCRIs under urethane infusion. Histopathological findings showed that the extent of myoglobin deposition increased on coadministration of BF with each drug. The correlation was found for myopathy risk evaluated by CPK level using the urethane infusion method and drug lipophilicity, ie., the water/n-octanol partition coefficient except for the case of SV. Histopathological findings for the kidney following HCRI treatment also reflected the CPK level in rats under urethane infusion.

Administration, Oral↗

PubMed2002

The effect of various substances on the suppression of the bitterness of quinine-human gustatory sensation, binding, and taste sensor studies.

The purpose of this study was to quantify the degree of suppression of the perceived bitterness of quinine by various substances and to examine the mechanism of bitterness suppression. The following compounds were tested for their ability to suppress bitterness: sucrose, a natural sweetener; aspartame, a noncaloric sweetener; sodium chloride (NaCl) as the electrolyte; phosphatidic acid, a commercial bitterness suppression agent; and tannic acid, a component of green tea. These substances were examined in a gustatory sensation test in human volunteers, a binding study, and using an artificial taste sensor. Sucrose, aspartame, and NaCl were effective in suppressing bitterness, although at comparatively high concentrations. An almost 80% inhibition of bitterness (calculated as concentration %) of a 0.1 mM quinine hydrochloride solution required 800 mM of sucrose, 8 mM of aspartame, and 300 mM NaCl. Similar levels of bitterness inhibition by phosphatidic acid and tannic acid (81.7, 61.0%, respectively) were obtained at much lower concentrations (1.0 (w/v)% for phosphatidic acid and 0.05 (w/v)% for tannic acid). The mechanism of the bitterness-depressing effect of phosphatidic acid and tannic acid was investigated in terms of adsorption and masking at the receptor site. With phosphatidic acid, 36.1% of the bitterness-depressing effect was found to be due to adsorption, while 45.6% was due to suppression at the receptor site. In the case of 0.05 (w/v)% tannic acid, the total bitterness-masking effect was 61.0%. The contribution of the adsorption effect was about 27.5% while the residual masking effect at the receptor site was almost 33%. Further addition of tannic acid (0.15 (w/v)%), however, increased the bitterness score of quinine, which probably represents an effect of the astringency of tannic acid itself. Finally, an artificial taste sensor was used to evaluate or predict the bitterness-depressing effect. The sensor output profile was shown to reflect the depressant effect at the receptor site rather well. Therefore, the taste sensor is potentially useful for predicting the effectiveness of bitterness-depressant substances.

Aspartame↗