Heat-resistant polycarbonate bottles were newly devised for autoclave sterilization of chlorhexidine digluconate solution, a disinfectant. To assess the usefulness in the clinical application, the shape transformation of the bottles and the chemical stability of their content of 0.05% chlorhexidine digluconate solution were examined after autoclaving in comparison with those of glass bottles and of their contents. The autoclaving experiment was performed at 115°C for 30 minutes. After autoclaving, the polycarbonate bottles increased slightly of less than 1.62% in outer diameter, whereas the change with glass bottles was unmeasurable. Levels of chlorhexidine digluconate and p-chloroaniline, its decomposition product, were determined in both types of bottles by high-performance liquid chromatography at 1 day and 1, 3, and 6 months after autoclaving. Levels of chlorhexidine digluconate remaining until 6 months after autoclaving were more than 98% and 97% in the polycarbonate and glass bottles, respectively. p-Chloroaniline was generated after autoclaving in levels of 0.02-0.90 μg/ml in the polycarbonate bottles and of 0.06-0.90 μg/ml in the glass bottles throughout the study. These results suggest that the newly devised polycarbonate bottles are resistant to heat and mechanical shocks, and that they are as useful as the presently used glass bottles for sterilizing and storing the chlorhexidine digluconate solution.

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Investigated for the purpose of developing a new dosage form for elderly patients were the effect of the gel concentration in preparation of the dry gel, the particle size of the dry gel, and additives in preparation of the dry gel on the water absorption and swelling behavior of a dry gel layer prepared with gelatin. Three principal results were obtained, First, the dry gel layer prepared at the 10% gel concentration demonstrated the fastest water absorption and swelling rate. Second, the water absorption and swelling behavior of the dry gel layer prepared at the 10% gel concentration was not affected by the particle size of the dry gel. Third, the water absorption and swelling rate of the dry gel layer was greatly increased by the more than 10% addition of sodium citrate in the amount of gelatin.

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We determined the methotrexate (MTX) concentration in sera of 15 patints with osteosarcoma using high performance liquid chromatography (HPLC). The patients were administered high-dose MTX in conjunction with leucovorin rescue therapy. The values obtained by HPLC were compared with those obtained by fluorescence polarization immunoassay (EPIA) (n=47), and a high correlation was observed (1.54 × 10^-7mol/1-1.70× 10^-3mol/1).
The MTX concentrations determined by FPIA and HPLC at 6, 24, 48 and 72 hours after initiation of the 6-hour intravenous infusion were analyzed by paired t-tests. No Significant difference was observed in the values at 6 and 24 hours between the two methods. However, the values at 48 (p<0.05) and 72 hours (p<0.0001) obtained by FPIA were significantly higher than those obtained by HPLC. The difference may be due to the presence of 7-OH-MTX, a metabolite of MTX, in these sera because the antibody crossreacts with this metabolite in this immunoassay. Caution should be taken in this FPIA interference.

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We studied, the effects of enzymatically modified stevia (Glycosyl stevia, SW) on medication compliance in 126 pediatric patients. SW is produced from Stevia rebaudiana Bertoni, its safety has been confirmed, and used in many, foods for sweetening. We mixed SW to a 0.5-1% concentration in powdered medicine and evaluated the effect of SW on patient compliance.
Medication: Before the SW addition, 42 subjects were administered medicines without sweetening as a powdered form, 14 subjects were administered it as a liquid form, and 70 subjects were administered it as a mixture with juice. After the SW addition, 99 subjects were adminnistered medicine as a powdered form. 20 subjects were given it dissolved in water, and seven subjects had it co-administered with juice.
Copmpiiance: Before the addition of SW for the 126 patients, 23% took their Medicine with out difficulty, 66.7%, managed to do: so with some Aevice or other, and 10.3% showed poor compliance. After, the addition of SW for the 126 patients, the compliance, significantly improved. About 80% of patients took their medicine without difficulty, 19% managed to do so with some device or other, and only 2.4% showed difficulty in improving their compliance. These results indicate that the addition of SW to powdered medicine is a useful method for the improving medication compliance in pediatrics patients.

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The variation in serum disopyramide concentration at early morning (6: 00) in inpatients administered 300mg per day of sustained-release disopyramide tablet (Rthmodan R, preparation A) or the same dose of non sustained-release disopyramide capsule (Rthmodan, preparation B) was studied. Twenty-one inpatients, whose mean age was 68.4 ±10.2 (SD) yr and mean body weight was 52.0±7.6kg, received preparation A (q 12 hr at 7: 00 & 19: 00). Nineteen inpatients, whose mean age was 68.3±12.9 yr and body weight was 54.0±11.3kg, received preparation B (tid at 7: 00, 12: 00 & 19: 00). No differences were observed in the mean ratio of serum disopyramide concentration at 6: 00 to dose between inpatients receiving preparations A and B, although a signficant difference was observed in its variation. When the intra-individual variability in inpatients monitored more than three times was compared, the CV was 4.93±1.74%(SD) in inpatients receiving preparation A versus 21.8±7.8% in inpatients received preparation B. Therefore, this suggests that the variation in serum disopyramide concentration in inpatients receiving preparation A was significantly decreased over that of preparation B.

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The inhalant solutions used in inpatients were examined in our study to see if they exhabit microbial contaminations. Also, using hospital pharmacists and non-medical staffs as the study subjects, the same examination was carried out on the inhalant solutions prepared for the outpatients. As a result, the samples used in inpatients were all found to be free from contamination. The samples used in the pharmacists showed no sign of contamination, when they were first preserved in a dark, cool place (4°C). However, among the samples preserved in a dark place at room temperatures, the contamination by Acinetobacter sp. was detected in the preservative-free mixture of tyloxapol 0.125% and physiological saline. The samples of the same preservative-free mixture used in the non-medical staffs were observed to be contaminated with various microorganisms like Enterobacteriaceae, even when preserved in a dark, cool place (4°C). Judging from the findings we obtained, the cool and light resistant storage conditions alone cannot prevent inhalant solutions from microbial contaminations without the addition of appropriate preservatives. The microbial counts and species of the contaminants vary according to the handling and environmental conditions of inhalant solutions. Therefore, for the safe use of inhalant solutions in in-and outpatients, the addition of preservatives is thought to be essential.

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The Endotoxin test was applied to detect endotoxin in the filtrates obtained using eight kinds of filter units employed for sterilization. The filtrate used in only one kind of filter unit was positive to this test. The concentrations of endotoxin in all of the filtrates were then determined by Limulus test using an ordinary reagent. In the filtrate that was positive to the endotoxin test, the endotoxin concentration was 0.873 EU/ml. On the other hand, in filtrates from the other filter units, the concentration was below the blank level. When endotoxin was determined in filtrates by Limulus test utilizing an endotoxin-specific reagent, in which a high concentration of endotoxin was detected, one of the five samples indicated a positive level, while the others demonstrated very low or blank level. These results suggest that even if the sample is positive to the endotoxin test, it is necessary to veify with the Limulus test utilizing endotoxin-specific reagent.

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We investigated the mechanism for diazepam sorptions into the ethylene-vinylacetate (EVA) copolymer membrane. A linear relationship was found between the amount of diazepam sorbed into the EVA membrane and the diazepam concentration when it was 5-20 μg/ml. The sorbed amount was influenced by pH. When the diazepam concentration in solution was 20 μg/ml, it was 0.17 mg/ g at pH 3.2 and increased to 0.74 mg/g at pH 7.0. Moreover, the experimental data showed a similar tendency as the calculated values, suggesting that the amount of diazepam sorbed was proportional to the concentration of the diazepam molecular form.

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We describe the process of legal prescription delivery used at Oita Medical University Hospital. This process involved three steps: development of a legal prescription printing system, arrangement of pharmacy and education of pharmacists in our pharmacy practice.
We developed a legal prescription printing system to be used in connection with our prescription ordering system in a total hospital information system called BUNGO. In this system, the correct prescriptions are printed automatically by printers located in each consultation room to ensure that the drug name, direction, dosage and prescribed days are checked each time they are ordered. The system allowed for a “Supplemental message (Gyomu-renraku)” to be prepared with each prescription.
Through the Oita City Pharmaceutical Association, 58 pharmacies that were permitted to receive legal prescriptions from Oita Medical University Hospital were selected and divided into seven blocks. Pharmacists who were working in these pharmacies were schooled in our method and technique of dispensing prescriptions during a 2-week course as a trainee of Oita Medical University Hospital Pharmacy and the importance of correct preparation at lecture meetings held every month by Oita City Pharmaceutical Association. Legal prescription reception desk “FAX corner” was set up by the association in the entrance hall of Oita Medical University Hospital with a pharmacist and two receiptionists stationed there to answer outpatients inquiries.
The number of legal prescription leaves gradually increased.

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Bactericidal effects of various disinfectants were examined in Aichi Medical University Hospital using clinically isolated methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MSSE), floor surface-isolated MRSA and methicillin-resistant coagulase negative staphylococci (MRCNS).
The results revealed following to;
1) Chlorhexidin gluconate was inferior to the bactericidal effects against all isolated strains.
2) Benzalkonium chloride was superior to the other disinfectants.
3) It seems probable that the bactericidal effect of iodophor was dependent on the length of acting time.
4) No significant difference in bactericidal effects was observed between MRSA and MRCNS.
5) In present study, Methicillin-resistant Staphylococcus saprophyticus indicated that it has a low sensitivity against various disinfectants.

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The disinfective effects of both ionic surface active agents sold in Japan were evaluated in antiseptic-resistant strains of methicillin-resistant Staphlococcus aureus. The four agents used in this experiment were TEGO®-51, HYPAL® No.20, HYPAL® No.5, and OBANOL (Mitsumaru). Minimum inhibitory concentrations (MICs) of OBANOL and HYPAL® No.20 were almost the same as all of the strains used by the broth dilution method. The MICs of HYPAL® No.3 and TEGO®-51 were higher than those of OBANOL and HYPAL® No.20. There was little difference in the MICs of the four agents to all strains used in the agar dilution methods. The MIC of OBANOL to antiseptic-high level-resistant strain was the same as that to the sensitive strains.
The effects of the concentration of the agents and the duration of exposure on the survival of the strains were also determined. The antiseptic-high level-resistant strain N20 was killed by OBANOL, HYPAL® No.20, and HYPAL® No.3 at the concentration of 0.031% within 1.5 minutes, but was not killed by TEGO®-51 under the same conditions. The effects of the four agents for disinfecting the hands were additionally evaluated. After 105 cells of bacteria were inoculated on hands, the hands were disinfected with the agents under the accompaning references. OBANOL killed all strains including the high-level antiseptic-resistant strain in three diferent experiments. From these results, the most effective agent for disinfecting against the high-level antiseptic-resistant strain among those agents used in this experiment was OBANOL.

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The effects of hot water and ozonized solution used for disinfection were evaluated in antiseptic-resistant strains of methicillin-resistant Staphylococcus aureus (MRSA). The viable counts of the antiseptic-sensitive and -low level-resistant strains were decreased to ≤10² cfu/ml by exposure to 60°C water within 2 minutes. However, the viable counts of the high levelresistant strain were not decreased to ≤10² cfu/ml by more than 5 minutes exposure to 65°C water.
The viable counts of the antiseptic-sensitive, -low level-resistant, and -high level-resistant strains were decreased to ≤10² cfu/ml by exposure to 70°C water within 30 seconds, 30 seconds, and 2 minutes, respectively. Sensitivity to hot water of antiseptic-sensitive derivatives, eliminated the antiseptic-resistant gene ebr, was higher than that of the original antiseptic-resistant strain. Sensitivity to ozonized solution of antiseptic-resistant strain was also lower than that of the antiseptic-sensitive strain. The viable counts of the antiseptic-high level-resistant strain were decreased to ≤10² cfu/ml by exposure to 1.5 ppm ozonized solution within 30 seconds.
These results clearly confirm that the antiseptic-resistant gene ebr was relative to a decline in the sensitivity to hot water and ozonized solution in antiseptic-resistant strains, and that 70°C water and 1.5 ppm ozonized solution are a useful means of disinfecting instruments and devices contaminated with antiseptic-resistant strains of MRSA.

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Investigated in seven Kosei-nenkin Hospitals (member hospitals of the Employee's Pension Insurance Society), were 24, 498 prescriptions given to outpatients. These were given to 21, 552 outpatients who were instructed to take medication on October 30, 1990 according to the prescriptions regardless of the various periods during which they have taken the drug. These prescriptions were accumulated from October 1 to October 30, 1990. In addition, 2, 021 patients who consulted the hospital's outpatient clinics on October 30, 1990 for treatment of their illnesses were interviewed at the dispensary to find out whether they were taking drugs prescribed by other medical facilities.
The results were as follows:
1) 549 (27.2%) of 2, 021 patients were taking drugs given by either other medical facilities or pharmacies.
2) The mean number of drugs prescribed in the 24, 498 prescriptions was 3.8 per patient. The number of drugs in anyone prescription was increased along with the age of the patient.
3) Overlapping of drugs among prescriptions were 724 (3.0%) cases in 24, 498.
4) 1, 706 (7.9%) of 21, 552 patients were given prescriptions containing a combination of drugs exhibiting a possible drug-to-drug interaction.
5) 840 (3.9%) of 21, 552 patients were instructed by doctors to take more than 10 kinds of drugs within the same day. The mean number of their illnesses was 4.5 (1-12) and that of drugs per one illness was 2.6.

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Kanebo Memorial Hospital has a unique computer system for facilitating patient care, making it an “intelligent hospital” . In the pharmaceutical occupation, prescription ordering system used by physicians for outpatients and inpatients has been in operation since May 1, in 1990. Since then Kanebo's new Medical Information System (MISK) has been established by the development of joint enterprise Kanebo Systems Laboratory.
The system is formed by the following components.
1) Medical histories of all patients.
2) Tablet counting and packing system (ATC) are connected by online network.
3) Drug information was identified by all positions.
4) Message delivering system painted surface information of adverse reactions and the problem of medical insurance system.
5) Drug inventory control system.

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Beta-methyldigoxin (MD), a new semi-synthesized cardiac glycoside, has been widely used for treatment of congestive heart failure. Since any dosage form other than tablet form is not commercially available for MD, it has been necessary to prepare powder by pulverizing the tablet when dose adjustment is required. It has recently been suggested that the loss of content in digoxin powder is caused by adhesion to the wrapping papers. In the present study, we examined the content-uniformity and adhesiveness of MD in powder by pulverizing. In addition, we investigated the effect of magnesium stearate, a lubricant, on the adhesion of MD to wrapping paper.
The content and content-uniformity of MD in powders were influenced by the numbers of tablet, namely, the amount of preparation. The extent of lost content and the variation in content-uniformity of MD increased with a decrease in the number of tablets. There was large adhesion of MD to wrapping papers. The percentage of MD lost by adhesion became exceedingly greater when the amount of powder per package became smaller. Furthermore, the percentage of MD lost in powder increased after dividing and packing by automatic machine, ranging from 17.1 to 37.3% of the initial value. When one package contained a small amount of powder, there was no remarkable effect of the lubricant on loss of MD after dividing and packing. This study confirms that attention should be given to prevent the possibility of MD content being lost in practical use.

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