Qualitative evaluation was made on Chinese medicine preparations: “Orengedoku-to” extracts. Quantities of the principal components were determined by high performance liquid chromatography and thin-layer chromatography-densitometry system. Composition of 17 commercial products (13 prescription drugs and 4 nonprescription drugs) was as follows (in mg/g): berberine 1.6-17.0, coptisine 0.3-5.0, palmatine 0.3-6.9, woogonin 0.03-9.2, geniposide 1.5-8.7.
Coptidis rhizoma, main component of Orengedoku-to, was examined for contents according to its origin. “Garene” originated in China gave the highest contents (in mg/ g): berberine 78.1, coptisine 30.5, palmatine 36.5. The qualitative test of Chinese medicine preparations, therefore, is very important at hospital pharmacy.

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Analgesic effect of Keishi-Ni-Eppi-Itto-ka-Ryo-Jutsu-Bu (KNE), a traditional herbal medicine against rheumatoid arthritis, on writhing reaction induced by acetic acid was investigated in mice. KNE, composed of gypsum, Zizyphi fructus, Cinnamomum cortex, Ephedrae herba, Paeoniae radix, Glycyrrhiza, ginger, Atractylodis rhizoma and hoelen, significantly depressed the writhing reaction, while Aconiti tuber, widely used for analgesic purpose, did not affect the reaction. The depressive action of each KNE component was examined. It was found that only Ephedrae herba showed significant dose-dependent depression of the writhing reaction. When the decocted liquid of Ephedrae herba was separated to aqueous layer and benzene layer at low pH, followed by high pH, the aqueous layer showed remarkable dose-dependent depression of the writhing reaction.

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To estimate pharmacokinetic parameters for individualized digoxin therapy, a method which is available to clinical practice was studied in 2 healthy volunteers and 4 patients with heart disease.
At the beginning of a once-daily regimen, the prescribed dose was administered and 9 blood samples were drawn in 48 hours without receiving the dose on Day 2, if possible. On Day 3, a routine digoxin therapy was started and to estimate parameters more accurately, several additional blood samples were drawn just before the next dose of digoxin for measuring the minimum digoxin concentrations (SGC) and 2 hours after the digoxin ingestion for maximum SGC.
The ability to predict SGC of this method based on repetitive dosing data was evaluated by comparing observed and predicted SGC. There was statistically significant correlation between observed and predicted SGC, where the prediction error was 11.9±9.4 (mean% S. D., n= 20). The method based on repetitive dosing data can be used in clinical practice, because fairly accurate parameters can be obtained by this method without interrupting a routine digoxin therapy.

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Three brands of chenodeoxycholic acid capsules of the companies A, B, and C were compared. One of the three brands shad very small weight deviation. Differential scanning colorimetry and scanning electron microscopy indicated that 2 brands contained crystalline drug and 1 brand contained amorphous drug. Gas-liquid chromatographic analysis of the extracts from bulk drugs and capsule formulations revealed that the 2 crystalline bulk drugs and the capsule formulations of the 2 crystalline drugs contained definite amount of ethyl acetate as residual solvent. The amount of the solvent in formulations might be reduced by purification of the bulk drug. Thinlayer chromatographic analysis of the extracts from the capsules indicated that small amount of materials other than chenodeoxycholic acid may be present in the formulations.

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Phase separation method has been applied to improve efficiency of magnetic control of ferromagnetic microcapsules. Ferromagnetic mitomycin C microcapsules (FM-MMC-mc.) were prepared by enclosing minimum ferromagnetic ferrite in mitomycin C microcapsules. On the other hand, FM-MMC-mc. was injected into the bladder of rabbits to treat the experimental bladder cancer which had been produced by transplanting V 2 carcinoma. As a result, antitumor effect of FM-MMC-mc. was remarkably higher fhan that of injectable MMC as control. Thus, the efficacy of FM-MMC-mc. was confirmed in this study.

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Stability of urokinase (UM) in sodium cefalotin preparations (CET) was investigated in terms of the agent's appearance, change of pH, and activity as determined by fibrin-plate Method and Chandler's Loop method. Electrophoresis was also used in the same study. The results are summarized as follows:
1) UM activity was significantly decreased after mixing. However, residual potency of CET remained above 96% even 24 hours after mixing. 2) UM was unstable in CET in various concentrations or IV infusions. Same tendency was observed with UM in standard CET. 3) From the results of electrophoresis, it was found that CET contained some foreign matters.
It was also found in the above study that CET or foreign matters in CET caused the decrease in UM activity. It is, therefore, concluded that UM is incompatible, with CET.

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A simple method for determination of sulpyrine content of suppositories with flame photometer was evaluated with use of 5 types of suppositories and one commercial suppository. The 5 suppositories were prepared by mixing 5 to 20% sulpyrine with cacao butter and Witepsol H-15 as bases. Each suppository was taken in a test tube containing distilled water, and shaken at 37°C for 2 hours. After cooling at room temperatue, the solidified base was filtered away. Sodium ion concentration in the remaining water layer was measured with flame photometer. The results obtained by this method were consistent with those by colorimetric assay, and the coefficients of variation were 1.0 to 3.1%. The distribution of sulpyrine in a suppository was also determined by this method. Thus, it can be concluded that this simple method provides a useful tool for the quality test in hospital pharmacy.

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Cause of coloration in an atropine sulfate eye drops was investigated. The eye drops prepared in our hospital pharmacy were returned by a 52-year old female patient after few days' use. No color change was observed in the same lot preparation stocked in the pharmacy. The patient was also given epinephrine eye drops and pilocarpine eye drops. Spectral changes of the colored eye drops suggested the presence of adrenochrome that is an oxidation product of epinephrine. Similar coloration was observed by addition of one drop of epinephrine eye drops to atropine eye drops. The conclusion was as follows:
The patient applied epinephrine eye drops first, and then atropine eye drops by squeezing the plastic eye dropper. As the dropper of atropine eye drops was restored to its original shape, a droplet of epinephrine eye drops left on the surface of the eye or eyelid was sucked into the dropper. Consequently, the stabilizer of epinephrine eye drops was diluted with sucked atropine eye drops and the oxidation occurred. The present case suggests the necessity of correct instruction to patient.

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Over-the-counter inquiries made by outpatients about drugs, collected in the period of September 1981 to July 1982, were analyzed. A total of 318 outpatients, consisting of 192 females (60.4%) and 126 males (39.6%), presented 322 inquiries. The time for answering the inquiries was measured in 203 patients. In 116 patients (57.1%) pharmacists' answers were finished within a minute, while in 3 patients (1.5%) it took more than 10 minutes. Contents of inquiries were classified into 8 categories. The most frequent inquiries were about dosage and directions for use of drugs, followed by those about quantities of drugs handed, and those about effect of drugs. The inquiries made by 35 patients (11.0%) were due to pharmacists' errors in dispensing and directions, and those by 19 patients (5.7%) due to the contents of prescriptions. This survey is closely related to the practice of patient-oriented pharmacies, and the data thus collected are useful for instructions given to patients and pharmacists alike.

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Physical properties, compatibility and handiness as determined by sensory test were compared between 20%Neuzym fine granules and current Neuzym granules. Both preparations met the respective requirements in the particle size distribution test. As for physical properties, improvement was noted in dispersibility of the fine granules. Compatibility was compared in terms of color, odor, moisture, and weight increase ratio as moisture index. No difference in evaluation of the above items was found between the two preparations except for wettability under severe condition of 30°C and 92% humidity. Handiness as determined by sensory test was found better with the fine granules than with the granules, particularly at the time of weighing and dividing. This result supports the prediction made on the basis of the data on physical properties.

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Stability and compatibility of water-soluble 20% lysozyme chloride fine granules used as oral liquid preparation were compared with those of a currently used syrup preparation. In the test for change on mixing performed in reference to the method of Kojiro et al., change with time in appearance, odor, pH, and lysozyme activity (by a bacteriolysis method) was examined.
Stability test for an aqueous solution demonstrated that this preparation is unstable in alkaline solutions but stable in acidic solutions, proving its usefulness as an oral liquid preparation.
Compatibility test showed that the preparation is not compatible, among the 21 kinds of respiratory, antiallergic and antibiotic drugs tested, with Bisolvon Syr., Conc. Brocin-Codeine Syr., Senega Syr., Atarax P Syr. and Cefro D. S. When the stability and compatibility of the preparation were compared with those of lysozyme chloride syrup, no apparent difference was observed.

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Pharmaceutical properties of 4 kinds of anti-inflammatory enzyme preparations were discussed. All preparations met JP X disintegration test and weight variation test. Activity of the enzyme dissolved by both rotating basket and paddle methods was compared within 120 min in pH 6.0 test fluid as enteric-coated films begin to dissolve. Activity curves of each product showed similar pattern in both methods. Product C was not disintegrated completely in pH 6.0 and 8.0 test fluids even after 120 min. To evaluate acid resistance of enteric-coated film of each product, activity of the enzyme dissolving in JP disintegration test fluids was measured. It is suggested that acid resistance of each product is satisfactorily kept in the 1st fluid, because its maximum activity in 2 nd fluid was equal to that in optimal pH range. Activity curve of the enzyme dissolving in pH shift test fluid was different from each other, and each maximum activity was nearly equal to that in optimal pH range. From these results, it is considered that 4 kinds of the preparations tested should have been kept under a quality control for acid resistance of the enteric-coated films. However, as core tablet of the product C was not satisfactorily disintegrated in test fluid studied, improvement on its disintegration property is needed.

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Compatibility of Bricef Dry Syrup (cefatrizine oral suspension) with oral liquids was investigated with regard to changes in appearance, pH value and residual potency. These changes were tested immediately, and 3, 7 and 14 days after admixing at room temperature, and in some admixtures, at 6°C.
At room temperature, decrease in residual potency during incubation was observed in admixture with concentrated brocin-codeine, brocin, and transamin syrup; however, the decrease was prevented at 6°C. A large decrease in pH was observed in the admixture with decreased potency. Consequently, a correlation between decrease of pH and potency may be considered. Significant change in appearance was not observed in any of the combinations tested.

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