Yuri Takahashi

Development of oral acetaminophen chewable tablets with inhibited bitter taste

Various formulations with some matrix bases and corrigents were examined for development of oral chewable tablets which suppressed the bitter taste of acetaminophen, often used as an antipyretic for infants. Corn starch/lactose, cacao butter and hard fat (Witepsol H-15) were used for matrix bases, and sucrose, cocoa powder and commercial bitter-masking powder mixture made from lecithin (Benecoat BMI-40) were used for corrigents against bitter taste. The bitter taste intensity was evaluated using volunteers by comparison of test samples with standard solutions containing quinine at various concentrations. For the tablets made of matrix base and drug, Witepsol H-15 best inhibited the bitter taste of the drug, and the bitter strength tended to be suppressed with increase in the Witepsol H-15 amount. When the inhibitory effect on the bitter taste of acetaminophen solution was compared among the corrigents, each tended to suppress the bitter taste; especially, Benecoat BMI-40 exhibited a more inhibitory effect. Further, chewable tablets were made of one matrix base and one corrigent, and of one matrix base and two kinds of corrigents, their bitter taste intensities after chewing were compared. As a result, the tablets made of Witepsol H-15/Benecoat BMI-40/sucrose, of Witepsol H-15/cocoa powder/sucrose and of Witepsol H-15/sucrose best masked the bitter taste so that they were tolerable enough to chew and swallow. The dosage forms best masking bitter taste showed good release of the drug, indicating little change in bioavailability by masking.

Effect of Sodium Caprate on the Absorption of Progesterone from Mixed Suppositories Administered to the Vagina of Rabbits

The promoting effect of sodium caprate (CAP) added to a progesterone mixed suppository was investigated in vitro and in vivo. The mixed suppository (S50), consisting of Witepsol W35 and ethylene-vinyl acetate copolymers (EVA40Y and EVA250); and a control suppository of Witepsol W35 (C50) were prepared by the fusion method. One or five percent of CAP was added to S50 and C50 containing 50 mg of progesterone. The release of progesterone from C50 was not influenced by the addition of CAP and there was no change in plasma level profile of progesterone after administration to the vagina of rabbits. On the other hand, S50 added with CAP showed rapid elevation of the plasma level of progesterone without any change in the sustained-release characteristics.

Biodistribution Study Using Egg Protein ELISA Kit after Administration of FITC-labeled Ovalbumin Solution and Its Double Liposomes in the In Situ Loop Method, and Its Implication in Oral Immunization

Ovalbumin (OVA) is often used as a model antigen, and its biodistribution is important for the induction of immunization, especially oral immunization. In this study, an allergic substance-detecting kit, Egg Protein ELISA kit, was applied to the investigation of the biodistribution of fluorescein isothiocyanate-labeled ovalbumin (FITC-OVA). After FITC-OVA solution and its double liposomes were administered into the intestinal loop with one Peyers patch, the biodistribution of FITC-OVA was examined with the Egg Protein ELISA kit. Each calibration was performed by fitting a quadratic curve to the observed ELISA response points. The ELISA response was almost the same between OVA and FITC-OVA. Similar ELISA response curves were obtained in Peyers patch (PP) homogenate, spleen (SP) homogenate and plasma (PL). The concentration of FITC-OVA could be determined at 4 - 64 ng/ml for aqueous solution and SP homogenate and at 1 - 64 ng/ml for PP homogenate and PL. Thus, it was suggested that the ELISA kit should be useful for measurement of OVA biodistribution in an oral immunization study. After the administration of FITC-OVA solution and its double liposomes into the intestinal loop, the biodistribution of OVA-FITC in PP, SP and PL was investigated. The distributed amount was the greatest in PP. At the early time, the distributed amount in PP, SP and PL tended to be greater with FITC-OVA solution than the double liposomes. FITC-OVA was retained longer in PP with the double liposomes than FITC-OVA solution. The present results indicated that OVA could transfer well to PP and systemic circulation even with the solution dosage form in the loop method, probably because it was not exposed to harsh conditions such as a gastric fluid. Namely, it implied that the protection from gastric pH and enzyme by the double liposomes, which had been reported before, would be importantly associated with the promotion of immune induction. In addition, the double liposomes could retain OVA longer in PP, which might cause the enhancement of oral immunization.

Dissolution Profiles of Glibenclamide Tablet Using Flow-Through-Cell Method

Operating conditions affecting the dissolution characteristics of glibenclamide were investigated with the flow-through-cell method (the third method of dissolution test in JP XIII). The partition coefficient of glibenclamide between octanol and phosphate buffer (pH 7.4) was observed to be 24.2, thus suggesting the lipophilic nature of glibenclamide. The flow indicator on the apparatus in the flow-through-cell method did not reflect the real flow rate of the dissolution media.The dissolution-time curve (ADT) value increased in line with the decrease in the beads diameter when the flow rate of the indicator was slow (8 ml/min). On the other hand, the ADT value was hardly affected by the beads diameter when the flow rate was fast (24 ml/min), however, a wide deviation in the ADT values was seen during such conditions. The operating condition of flow rate and beads diameter was optimized based on the response surface method. As a result, a flow rate of 14 ml/min and a bead diameter of 0.5 mm were estimated as the optimal conditions to obtain the largest ADT and the smallest deviation in the ADT. When using the fl ow-through-cell method, the operating condition should be optimized based on the nature of pharmaceuticals under test.