Quality of high-molecular-weight substances was tested by thin-layer gel filtration chromatography (TLGC). Preparations selected for the tests were those of lysozyme chloride, urokinase, serratiopeptidase, cytochrome c, trypsin/α-chymotrypsin, trypsin/bromelain, streptokinase/streptodornase, and insulin. Pharmacia TLGC apparatus was used for the analysis. A 0.025M phosphate buffer system (pH7.4) containing 1.5% sodium chloride was mainly used as developing solvent, and nigrosine as color developing agent. A good reproducibility was demonstrated in the tests by the TLGC. It was found that the TLGC, simple and convenient in operation, is a reliable method of analysis for the quality control of these preparations.

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The serum levels of antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, primidone and sodium valproate) in children was determined by enzyme immunoassay and gas-liquid chromatography. The relation between the serum level and the therapeutic dose, and the interaction of antiepileptic drugs were studied. The drug concentration in serum must be measured in the check of adverse drug reactions and in the determination of therapeutic dose. In the multiple-drug administration, it is difficult to determine the most effective drug from among the drugs combined. But the single-drug therapy is free from causing drug interaction and makes it easy to reduce the dosage of antiepileptic drugs in the process of treatment.

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Three potent anticancer drugs, mitomycin C (MMC), adriamycin (ADR) and carboquone (CQ), were microencapsulated with ethylcellulose in the principles of coacervation with certain modifications and the microcapsules thus prepared were examined with the scanning electron microscope. It was demonstrated in vitro and in vivo experiments that the release of action of microencapsulated MMC was made sustained and long lasting. The in vitro release of ADR and CQ from the microcapsules was also examined.

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Effect of various injections on the stability of ascorbic acid (AsA) was investigated by quantitative analysis of AsA and dehydroascorbic acid (DAsA). In the study, 23 kinds of injections, which were added frequently to infusion solutions in combination with AsA, were selected in consideration of practical conditions in hospital. Among these injections, the following increased significantly the oxidation of AsA in infusion solution: 20mg riboflavin phosphate sodium (B₂), 10mg flavin adenin dinucleotide phosphate, 30mg pyridoxal phosphate, 1, 000μg hydroxocobalamin, 500μg cobamamide, multi-vitamin injection (Vitamedin, Vitaneurin) and trace element injection for intravenous hyperalimentation (IVH-M₂). When exposed to indoor sunlight (2, 000lux, 6hrs), residual ratio of AsA was 64% in the presence of B2 and 44 % in the presence of IVH-M₂, compared with 94% in case of no addition. As the main degradation product of AsA in infusion solution, DAsA was identified by isotachoelect rophoresis.

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Plasma theophylline concentration of a slow-release theophylline preparation (SRT: Theona P) was measured by high-pressure liquid chromatography. SRT was administered to 6 healthy adults orally in dose of 100mg. Dissolution test of SRT by the rotating basket method made in accordance with U. S. P. XVIII revealed that the drug tended to dissolve slowly, dissolution rate being about 50% 6 hours after initiation of the experiment. The experiment also demonstrated that plasma concentration of theophylline reached peak about 5 hours after oral administration of SRT on the average, and about 2 hours after use of Aminophylline Tablet (immediate-release preparation).
Average maximal plasma theophylline level was 1.32μg/ml for SRT as compared with 1.92μg/ml for Aminophylline. In clinical trial, the plasma concentration of theophylline was not maintained at 10μg/ml after oral administration of SRT and Aminophylline Tablet in dose of 100mg 4 times a day, respectively. The 10-μg/ml level was maintained when SRT single dose was increased to 200mg.

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Slow-release aminophylline tablet (SR-AP) showed a marked tendency to dissolve slowly in the in vitro studies, dissolution rate being about 80% 9 hours after initiation of the experiment. Pharmacokinetics of theophylline was studied with 12 healthy adults. SR-AP was administered in dose of 3.01±0.44 mg/kg as theophylline and immediate-release aminophylline tablet (AP) in dose of 3.05±0.54 mg/kg. Plasma concentration of theophylline was measured by high-pressure liquid chromatography. Plasma theophylline level of SR-AP reached peak 7.7±1.4 hours after oral administration, as versus 2.0±0 hours for AP. Maximal plasma theophylline level averaged 4.34±0.92 μg/ml for SR-AP compared to 4.87±1.48 μg/ml for AP. When the serial plasma concentration data were analyzed by the one-compartment model, the mean value of the elimination rate constant (β) was 0.0742±0.0214 hr^-1 for SR-AP and 0.1599±0.0214 hr^-1 for AP. An average area under the curve (AUC) of SR-AP was about 2.5 times AUC of AP. It was thus suggested that SR-AP has enough potency to maintain therapeutic plasma level.

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Two commercial 5-fluorouracil injections (A and B) were tested in time course for their stability during storage. Appearance, coloring, pH, content of 5-fluorouracil and decomposition products by TLC were followed every two months through the 2-year storage of A and B at room temperature, 35°and 40°. After the 2-year storage at room temperature, both A and B retained about 94% of their contents and showed no change in pH and in appearance, proving that they are comparatively stable. But at 35°, yellow-brown color gradually developed in the products, pH values declined and contents of 5-fluorouracil reduced to 80%. At 40° these changes were accelerated and finally produced brown solutions. Decomposition products, observed by TLC, were found to be in more than 6 kinds.

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The method to estimate hygroscopicity of pharmaceutical products in powder or granule has not been established. In this study, changes in weight and fluidity of 10 commercial dry syrup preparations (fine granules to be prepared into a liquid form) were examined after storage with and without addition of sulpyrine powder. The samples were stored in 8 grades of relative humidities ranging from 56.3 to 100.0 % at 30°. When the data from each of the samples were plotted with weight increased (%) as ordinate and relative humidity (%) as abscissa, the hygroscopic curves were obtained respectively. From the curves, 3 kinds of values (θ, RHs, RHs') were selected to indicate the characteristics of hygroscopic changes of each sample. These values were considered representative of hygroscopicity of powders or granules unless formulations were changed. For protecting them from environmental water after repackaging, diluting or mixing with another product, they should be stored in the condition of lower humidity than RHs.

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Piperacillin sodium for injection (1-g potency), a synthetic penicillin preparation, was investigated on its change with time in appearance, pH and residual potency after its addition to some intravenous infusions together with various kinds of injections. A total of 54 admixtures of 34 commercial injections combined frequently with synthetic penicillins were used.
There was no visible recognizable change in appearance of any admixture. In one admixture, the pH passed the stable range of components within 6 hours. There were 2 admixtures in which the residual potency decreased below 90% 8 hours after mixing. Besides the 3 admixtures mentioned above, there were some others which were questionable as to their compatibility.

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