Incompatibility of Cabagin-U Kowa granule with each one of 61 kinds of drugs, which is often used in combination, was studied. The main ingredient of Cabagin-U, methylmethionine sulfonium chloride (MMSC), is hygroscopic by itself. In this study the substance apparently showed an increase in hygroscopicity when mixed with ascorbic acid, magnesium oxide and sodium bicarbonate. But it was found from the analysis of the hygroscopicity curves that the degree of moistening of the mixture corresponded to the arithmetic accumulation of hygroscopicity of each component combined. By the thin-layer chromatography, 3 spots of decomposed components, homoserine, methionine and an unidentified substance, were detected in the mixtures. The rate of decomposition of MMSC allowed for 2 weeks at 20° and 65% RH was approximately 6% in combination with sodium bicarbonate, 1% with magnesium oxide and more than 10% with ascorbic acid.

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It often happens that an outpatient is given too many kinds of drugs on prescriptions issued from two or more departments. We investigated into the tendency on the basis of 7, 196 prescriptions issued to the outpatients in a month. Major findings. 1) 206 outpatients were given prescriptions from two or more departments; 2) 82% of them were pre scribed at two departments, and 5% at more than 4 departments; 3) patients given 7 to 9 kinds of drugs formed the largest group and there were some given about 20 kinds; 4) patients who had received drugs of same effect accounted for 16.6%; 5) 5 patients received drugs in contraindication and 16 were given drugs requiring caution in concomitant use; 6) patients prescribed drugs producing interactions that may cause adverse reactions made up 3.0%. In view of these findings, it is essential for ensuring safety in medical treatment to keep close cooperation not only among physicians, but between physicians and pharmacists. Further, a system should be established for identifying patients treated at two or more departments and their prescriptions.

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A test method to check the dissolution pattern of timed-release preparations is described. Rotation method of U. S. P. XIX was used as a dissolution tester. First, 900ml of dissolution medium containing 2.0ml of diluted HCl and 2.0g of NaCl in 1000ml was used. By exchanging 5 ml each of the medium with the same volume of the second solution (disintegration, J. P. IX) at the intervals of 10 min for the first 1hr and of 15 min for the subsequent 4 hrs, pH of the medium was designed to change gradually from 2.3 to 3.5 in the first 150 min, rapidly from 3.5 to 5.7 in the following 30 min, and gradually up to 6.5 after 300 min, volume of the medium being kept at a fixed level. The rotation rate of basket was 100 rpm. Under the above condition, dissolution curves of iron preparations in 5 dosage forms of different manufacturers were compared. Maximum dissolution percentage varied from 27 to 92% among samples. At about pH 4, precipitates were formed in the medium as a result of the decrease of solubility of iron into the medium. The rates of dissolution of 6 dosage forms in the same lot number in the first 120 min varied largely, from 5 to 20%.

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Stability of urokinase activity in the presence of following adjuncts was studied in various infusions at room temperature: mannitol, human serum albumin (albumin) and hydrogenated castor oil polyoxyethylene 60 mole ether (HCO-60). Urokinase activity was stable in the saccharum infusions. In the electrolyte infusions the activity was imediately and considerably decreased but recovered to the level of the control by dialysis. As a result of the analysis of variance of adjunct effect, it was suggested that urokinase activity in the presence of albumin was more stable than in the presence of mannitol. Albumin and HCO-60 prevented urokinase from adsorbing to plastics and glass in the rotation, vibration and drip infusion test by thetube method. Albumin is a human protein having no blood coagulation factor, while HCO-60 has unknown pharmacological action. For this reason, albumin is a better adjunct to urokinase than mannitol and HCO-60.

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The color of sulpyrine solutions grew in parallel with the concentration of sulpyrine and by addition of lysozyme chloride. The pH values of these solutions rose with time (t) as: pH=k log t. However, when acidic compounds were added to them, the rate of the change of pH values was decreased, and the coloration was controlled. In this case, k values as the rate constant were changed at about pH 2 and 2.6-3.2, and light color developed in the process of rising of pH values of the solutions above 2.6-3.2. These results were contrary to the properties of sulpyrine observed in decomposition to 4-methylaminoantipyrine in known solutions. Aldehyde was detected from coloring on the spot in thin-layer chromatography by Schiff's reagent. Therefore, it was considered that the colored matter was formylic compounds produced from residual sulpyrine without change at fourth position.

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Compatibility of r-oryzanol fine granules (20%) with 101 commercial preparations was tested under three conditions of constant temperature and relative humidity (A: 30°, 92%; B: 25°, 75%, and C: 5°, 52%). As a result, 64 of the 101 preparations did not show any change in appearance without packing under conditon A for 28 days. Incompatibility was found in 13 preparations but, except aminophylline, many preparations are thought to be compatible for a limited period, when sufficient care is taken for storage. In other 13 preparations changes were inhibited by compounding, and 11 preparations showed changes similar to those in single ingredient preparations used for control.

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Close investigation is essential in the study on dispensing errors. In the study under the same inspector of dispensed medicines, the number of dispensing errors per day showed close relationship with the number of prescriptions filled per day. The risk of dispensing errors can be expressed as: A/B×100 (where A is the number of dispensing errors and B theoretical value of dispensing errors). The daily error rate (ie, rate of the number of errors detectable per day to the number of prescriptions filled per day) was changed far and wide, and the error rate by day of the week did not show statistically significant difference.

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Many antibiotic preparations for intravenous injection are available in soluble salt type. Na mEq in the mixture of lactated Ringer's solution and several antibiotics have been measured. Carbenicillin disodium and sulbenicillin disodium increased Na mEq as much as 15-16% against the theoretical values. That increase should not be disregarded.

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It has been known that 10-20 % of patients on α-methyldopa therapy become positive to Coombs' test and some of them develop autoimmune hemolytic anemia. In Japan these cases are rarely reported (only 5 of 1, 064 patients treated with α-methyldopa). Adverse reactions to α-methyldopa in 93 outpatients were studied. None of the patients showed positive Coombs' test and clinical signs of hemolytic anemia, but other adverse reactions occurred in some patients.

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