Masanori Iwata

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.

ウイテプゾール, エチレン-酢酸ビニル共重合体混合系新規基剤を用いたプロゲステロン坐剤

A sustained release suppository containing progesterone (mixed suppository) was prepared to treat the luteal phase defect. A mixture of ethylene-vinyl acetate copolymer (EVA) and Witepsol-W35 was used as the suppository base. Characteristics of the mixed suppositories using various types of EVA were compared with those of Witepsol-W35 alone (control suppository). Determined as physical characteristics were hardness, DSC peak temperature, heat of fusion and release profiles of progesterone. Furthermore, the plasma concentration profiles of progesterone observed from suppositories were measured in rabbits. The sustained release of progesterone from the mixed suppository was observed in the beads cylindrical filter method. When the mixed suppositories were administered to the vagina of rabbits, some part of the suppository remained after 3 hours though nothing remained the control suppository. The Pharmacokinetic parameters obtained from the plasma concentration profiles suggested the sustained release property of progesterone in the biophase when the mixed suppository was administered. With this mixed suppository, the concentrations of progesterone in the vagina, cervical canal and uterus at 3 hours after the administration were higher than those of the control suppository. These results suggest that the mixed suppository could be useful as a dosage form for replacement therapy of progesterone.

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.

Current State of Drug Information Services in Japan. Based on a Hospital Survey in Kanagawa Prefecture.

The rapid growth of pharmaceutical care in Japan has resulted in the need for a new clinical support system for drug information (DI) services. The DI committee of the Kanagawa Society of Hospital Pharmacists conducted a survey of hospitals in 1997-1998. The purpose of the survey was to determine such things as the number of pharmacists actually working in DI, the number of hospitals publishing a DI newsletter and also the number of hospitals utilizing computer automation in their DI programs. The survey consisted of 16 questions that were mailed to 353 hospital pharmacies, out of which 155 responses were returned. The results of the survey were compared to the findings of a similar study performed in 1996. One hundred-two of the 155 pharmacies (66%) indicated that they had a DI-room within their facility. Eighty-five percent of the facilities had their own hospital formulary. In addition many (56.8%) of the DI-rooms had a computer system, but on the other hand only 11.0% of all institutions used it for computer communication and literature seachs such as for MEDLINE. As changes occur in the medical environment, the DI related job should respond accordingly. An average citizen can now access much DI through the Internet, but the qualify of that information may be suspect. The problem today is how to encourage the hospital pharmacies to also access the Internet and both use and evaluate the huge amount of DI that is to be found there.

Preparation of Zinc Pyrithion Lotion as a Hospital Preparation and Evaluation of its Physical Characteristics.

In order to treat psoriasis, many kinds of drugs are administered systemically and topically. However, the topical admimistration of drugs is preferred to the systemic administration because the former can occasionally cause serious side effects. Zinc Pyrithione (ZPT), which is recognized as an active ingredient in a major anti-dandruff shampoo, was introduced as a new antipsoriatic agent. In this study, ZPT lotions as a hospital preparation were prepared for topical administration.Hydroxypropylcellulose-H (HPC), sodium-polyacrylate (PANA) and carmellose sodium (CMC) were used as a suspending agent of 0.5% ZPT lotion. The following physical characteristics, the viscosity, the osmotic pressure, the sedimentation, the microscopic view and the dispersion were investigated in each ZPT lotion containing different suspended agents.The viscosity of the ZPT lotion with HPC and CMC increased with the additive ratio of these suspended agents. On the other hand, the viscosity of the ZPT lotion with PANA increased logarithmically with its additive ratio. The low osmotic pressure of each lotion was expected to be less irritable in clinical application. When ZPT lotions were stored at room temperature for 14 days, the lotion with HPC or CMC showed free sedimentation and caking of the particles. In contrast, the lotion with PANA showed a growth of particles by a microscopic analysis and coagulated sedimentation by macroscopy. These phenomena may be due to the ionic intensity of the solution and the interaction between ZPT particles. The dispersion time of ZPT lotions with PANA was shorter than those with HPC or CMC.Based on our findings, 0.2% PANA was found to be preferable to HPC and CMC as the suspended agent in ZPT lotion.