The stability of halothane stored in five different vaporizers for a week was studied by gas chromatography (G.C.). An impure material of low boiling points was detected in halothane whichwas kept only in a particular vaporizer. The impure material increased to be detectable within 30 minutes after halothane was transferred into thevaporizer. After 3 months, the level of the impure material exceeded 0.005% which was the maximum allowable amount for volatile impurities regulated by Pharmacopoeia of Japan. Thenature of the impure material was not known.
On the other hand, the impure materials of high boiling points were detected in all vapori zers. GC-MS analysis indicated that these materials were brominated thymoles, suggesting that halothane was dissociated and the released bromide reacted with thymole, a disinfectant. Amounts of the materials of high boiling points increased by irradiation with white light and the halothane colored yellow.
The halothane manufactured 30 years ago and kept in a sealed brown bottle was also tested for its stability. In this halothane, although it was so old, noimpure materials of high boiling points or yellow color was observed. These results suggested that halothane was unstable in a vaporizer especially when exposed to light. Therefore, the remained halothane should not be left in the vaporizer.

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Rifampicin (RFP) gels were prepared with a new gel base consisting of polyglycerol ester (PGE), glycerin and oil. PGE used was decaglycerol ester (DGE) that was a monoester compound of decaglycerin and one of either lauric acid, myristic acid, stearic acid or oleic acid. Oils used were liquid paraffin, isopropyl myristate, isostearyl palmitate, octyl dodecanol and glycerin tri 2-ethyl hexanoate. 24 kinds of RFP gels were obtained by combination of these DGE and oil. These RFP gels were compared for their physico-chemical properties of stability, viscosity, hardness and dissolution rate. The results were as follows:
1.The preparation of RFP gel using a DGE gel base was affected by the kind of DGE and oils used. It was also affected by addition of propylene glycol. 2. The stability of RFP gel was affected by the kind of DGE and oils used and by the addition of propylene glycol. 3. The combination of DGE and liquid paraffin, or glycerin tri 2-ethyl hexanoate was more stable than others. 4. It was predicted that a concentration range of the optimum stable combination of DGE, oil and other additives existed in all RFP gels. 5. It can be assumed that these RFP gels possess the properties of ointment.

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The effects of age and concurrent administration of antiepileptic drugs on phenobarbital serum concentration/dosage ratio in children were studied. The ratio of serum concentration/dosage for phenobarbital both without and with the concurrent administration of antiepileptic drugs was significantly correlated with the age of patients, and the ratio increased with the increase in the age of children. The ratio of patients who had taken valproate sodium and/or more than two kinds of anti-epileptics with phenobarbital washigher than that of patients had taken phenobarbital alone.
Therefore, the patients who are taking valproate sodium and/or more than two kinds of anti-epileptics with phenobarbital is needed careful monitoring of phenobarbital serum concentrations because of their drug interaction.

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The relationship between dose and serum concentration of sodium valproate (VPA) was studied in epileptic patients who had received VPA alone chronically. Data of the epileptic patients (in-or out-patients, patient name, age, weight, sex, drug name, dose, serum concentration, dose number per day, sampling time, hepatic and renal function, compliance and seizer control) was putted into a micro-computer as DATA BASE.
Blood samples were obtained within one to six hours after the dose in the morning from 203 patients with normal hepatic and renal function, their ages ranged from 0 to 80 years. We divided them into 5 age groups (0≤Y<6, 6≤Y<12, 12≤Y<18, 18≤Y<50, 50≤Y<80 years) from a consideration of different dose (mg/kg/day) to investigate a correlation between dose and serum concentration of VPA in each age group.
Regression analysis in these 5 age groups varied greatly. Pediatric groups (0≤Y<12 years) and geriatric group (50≤Y<80years) appeared to have a lower correlation compared to adult groups (12≤Y<50 years).We speculated that this poor correlation was due to interpatient variability, dosage form and foods in the gastrointestinal absorption, poor compliance in pediatric groups, and to lower protein binding in geriatric group.

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Susceptibility of 353 bacterial strains, composed of 6 genera and 9 species, which were isolated recently from various clinical materials in Yamagata University Hospital, to 4 disinfectants, chlorhexidine gluconate (CHG), benzalkonium chloride (BAC), saponated cresol (SAC), and povidone iodine (PVP-I), was examined.
1.All of the clinical isolates tested were sensitive to SAC and PVP-I, however, susceptibility of the isolates to CHG and BAC varied from species to species and also from strain to strain. 2.Most of the strains Serratia marcescens, Pseudomonas cepacia, Proteus mirabilis and Pr. vulgaris seemed to be insensitive to CHG, though they were sensitive to BAC.3.Many strains of Ps. cepacia were resistant to not only CHG, but also BAC. 4. Most of the strains of Staphylococcus aureus, Sta.epidermidis, Escherichia coli, Klebsiella pneumoniae, and Ps. aeruginosa were estimated to be sensitive to CHG and BAC.
These results indicate that the resistant strains against CHG and BAC at the concentration recommended for disinfection of are be existent in some species of gram-negative bacteria of clinical isolates.

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To evaluate the pharmaceutical properties of five kinds of cataplasms, adhesive force, release pattern of methyl salicylate (MS) and water content in cataplasm and percutaneous absorption behaviors of MS were investigated in vitro and in vivo.The results obtained were as follows:
There were a remarkable differences among the products in the adhesive force and release profiles of water after application of cataplasm in humans.In vitro release rates of MS through a cellophane membrane from cataplasm increased with an increse in the content of the drug prescribed.The concentrations of salicylate in the serum and the tissue (skin and muscle) after application of the cataplasm in rats also increased with an increase in the content of the drug.Furthermore, the serum concentrations of salicylate after application to the stripped skin of rats were considerably higher than those to the intact skin of rats except for one product.
These results indicate that MS can be absorbed in proportion to its contents and the stratum. corneum acts as a barrier to the percutaneous absorption.The differences in these pharmaceutical properties of cataplasm suggests the possibility of making a difference in feeling upon a touch on the skin or the efficacy in stupe among them.

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Fluorescence polarization immunoassay (FPIA) with TDX^® system for the determination of serum cyclosporine (CsA) concentration was evaluated and compared to radioimmunoassay (RIA) and high performance liquid chromatography (HPLC) using 24 samples obtained from bone marrow transplant patients. The within-run and between-run coefficient of variance were less than 6%. The correlation coefficient between the measurements by FPIA and RIA, or that by FPIA and HPLC was more than 0.98. FPIA seemed to be useful for therapeutic drug monitoring of CsA. However, serum CsA concentrations by FPIA and RIA were higher than those determined by HPLC.
The results suggest that the metabolites of CsA cross react with the antibodies of FPIA and RIA kits. Since there is little information about the immunosuppression and toxicity of CsA metabolites, it may be important to select a suitable assay method for the purpose.

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At present the blister package of “press through packaging” (PTP) style is widely adapted for tablets and capsules in Japan. Using original reports that was searched out with the “IGAKU-CHUO-ZASSHI” (Japan Centra Revuo Medicina) from 1981 to 1986, We statistically observed a number of patients for PTP foreign bodies in esophagus. The statistics showed that the number of patients showed an increasing tendency in Japan. The age's population of patients was mainly distributed among the years 40 to 70, and there were more female patients than male patients. Most patients recognized that the PTP played the only role as the package for tablets and capsules. These facts suggest the necessity of phamacist's consultations to the patients.

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Among the commercial tablets having breaking lines, there are very hard ones which are difficult to be broken into halves by fingers. A device was designed to make a break such hard tablets into halves easily. The device consisted of four acrylic plates connected with three hinges. The cutting procedure was as follows:
(1) place a tablet on a central hinge to make an edge of the upper acrylic plate coincident with a breaking line of the tablet;(2) sandwich each half of the tablet between upper and lower acrylic plates;(3) bend the central hinge down.According to this procedure, the tablet was broken into halves smoothly. Samples from six commercial hard tablets were employed, three of which were considered to be too hard to break into halves by fingers in some hospitals.
In comparison with manual breaking, it was found that this device could break hard tablets into halves simply and more exactly. These results suggest that this device for cutting a tablet into halves is very useful tool for the prescription work in hospital pharmacy.

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Dissolution behavior of a newly designed, commercially available sustained-release tablet of theophylline containing 50mg (Theodur^® 50) was measured according to the J. P. X dissolution test procedures in pH 1.2, 6.8, and pH1.2 adding 0.25% Tween 80 solutions.
The following results were obtained: The release from Theodur® 50 was pH-independent, but was much affected by wet and rotating velocity of dissolution test.The required time for 50% dissolution at 100rpm was about 2 times as large as at 200rpm.

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Ferromia^® Granules is a newly developed medicine for iron deficiency anemia that contains sodium ferrous citrate as an active ingredient. 23 kinds of drugs (e.g., vitamins, anti-ulcer drugs, digestants, antacids, purgatives and antidiarrheals) which may be admixed with Ferromia^® Granules were tested for compatibilities, determining the changes in appearance and the moisture absorption.The drug samples were wrapped in polyethylene-laminated glassinepaper and preserved at 25°C with 75%RH for 30 days.
No change in the appearance of Ferromiaio was observed in its admixtures with 21 drugs, but when admixed with HICEE Granules or sodium bicarbonate, Ferromia^® Granules became brown. This change was considered to result from incompatibility. On investigation it was found that the change in color was due to a reaction of L-ascorbic acid in HICEE Granules with sodium ferrous citrate in Ferromia^® Granules. Ferromia^® Granules was not hygroscopic by itself and it was shown that the extent of moisture absorption by admixtures of Ferromia^® Granules with other drugs was almost the same as that of each particular drug.

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