5% aqueous solution of so-called “sodium hexametaphosphate” (HMP) has been used clinically as a direct solubilizing agent of bile pigment calcium gallstones for more than 20 years. This solution has been found to he highly safe and to possess an excellent chelating action under a normal physiological condition. Since HMP is unstable in an aqueous solution, the preparation must be prepared just before clinical use. Further, it is very difficult to dissolve HMP in water and to adjust the pH of the solution.
To overcome these difficulties, a new method for preparing HMP solution is used successfully. A commercially available HMP powder is dissolved in 7 % sodium bicarbonate solution to make 5% solution and filtered through a Milipore filter (pore size: 0.22-0.45μm) to eliminate bacteria and other contaminants. These procedures are simple and easy enough for dissolution and pH adjustment, and thus the solution may be prepared easily at any institutions just before infusion into patients with cholelithiasis.

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The reliability of substrate-labeled fluorescent immunoassay (SLFIA) method was examined using amikacin sulfate (AMK) samples of 5 known concentrations in spiked serum. The result of this SLFIA method were compared with those of enzyme-multiplied immunoassay technique (EMIT), radioimmunoassay (RIA) and bioassay methods. The correlation coefficient of the SLFIA method was 0.9999 and the regression line was Y=1.116X + 0.069. The correlation coefficients of the EMIT, RIA and bioassay methods were more than 0.999. The within-day and between-day coefficients of variation of the SLFIA assay were 2.82-9.13% and 3.04-8.14%, respectively. In AMK-spiked serum samples, the correlation coefficient between the SLFIA and EMIT methods was 0.9996, and the regression line was Y=1.137X-0.181. The value of SLFIA was slightly higher than that of EMIT. Compared with SLFIA and RIA or bioassay, the high correlation was also obtained in AMK-spiked serum samples. In serum of patients undergone AMK therapy, furthermore, the results obtained by SLFIA were compared with those obtained by EMIT, RIA and bioassay. These showed high correlation with each other, though, the value of SLFIA was slightly lower than those of other methods. These results suggest that the SLFIA method may be used for the routine clinical monitoring of serum AMK.

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Dissolution and absorption of 2 brands of griseofulvin preparation (A and B) and an inproved form of the preparation B (C) were compared. Dissolution test was made by using Sartorius Solubility Simulator. As an eluate, about 30% ethanol solution was used, because griseofulvin is insoluble in water. Amount of griseofulvin was determined by HPLC. Absorption study was made using rabbits. Plasma concentration of griseofulvin was determined by spectrofluorometer. The following results were obtained: 1) In dissolution test, 50% dissolution time of preparations A, B and C were 49 min, 63 min and 37 min, respectively. Dissolution rate at 120 min was high in the order, C>A>B, where the rate of C was significantly higher than that of the other 2. 2) In absorption test, plasma concentration of A reached its maximum in 8 hours after administration, but that of the other 2 in 6 hours. Plasma concentration of B was generally lower than those of the others.

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The dissolution patterns of cefadroxil in capsules were examined according to the JP X dissolution test. Cefadroxil capsules of brands A and B exhibited low dissolution rates of the drug and no disintegration was observed in 60 min. On the other hand, another lot of each brand supplied subsequently showed rapid disintegration and the dissolution of the drug almost completed in 30 min. A hydrophobic lubricant, magnesium stearate and the like was considered to suppress the disintegration and the dissolution of the drug in the former cases.
It was also found that vigorous shaking of the capsules suppressed the disintegration and the dissolution of the drug in one lot of capsules which showed rapid disintegration and dissolution of the drug before shaking.
It was, therefore, concluded that the dissolution of cefadroxil in capsules can be remarkably suppressed when a hydrophobic lubricant is used. It is important to control carefully the amount of the lubricant, mixing time of a mixture of drug, diluent, and lubricant before packing, and the physical condition at the time of transportation or storage.

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The irritative effects of 10% phenobarbital (PH) and phenobarbital sodium (PHS) solution for injection, 5% pentobarbital sodium (PES) solution for injection, 10% thiopental sodium (THS) solution for injection, and 5% chloral hydrate (CHH) solution on the rectal membranes of rabbits were examined wit h and without optical and scanning electron microscopes. Little irritation was observed after administration of PHS, THS, and CHH. However, PH and PES caused severe and mild irritation on the rectal membranes after rectal administration, respectively. Irritative effects of PH and PES may be attributed to organic solvents contained in these compounds

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Comparison between the original decoctions of “Toukakujohki-toh, ” one of the commonly prescribed formulas in oriental medicine, and the granules of the extracts of 6 commercially available brands was studied on the following subjects;1) Contents of cinnamic aldehyde, cinnamic acid and glycyrrhizic acid;2) TLC profiles of the freeze-dried decoction and of the granules extracted with n-hexane, chloroform and methanol;3) Effects on blood coagulation and fibrinolysis in vitro. In all of the six brands, the total amount of extracts in the daily dose was smaller than 1/3 of the original decoctions. Especially, volatile compounds in the granules such as cinnamic aldehyde and cinnamic acid were remarkably reduced as compared with those in the decoctions. The TLC profiles of 2 preparations, decoctions and granules also showed a difference from each other.
It was indicated that the effects of the granules of Toukakujohki-toh extracts on coagulation measured in prothromdin time and activated partial thromboplastin time and on fibrinolysis of urokinase measured by fibrin plate method were only 10% of the effects of original decoctions.

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As an agent for injection sclerotherapy (endoscopic embolization) for esophageal varix, an injectable solution (EOMA) was prepared by mixing ethanolamine oleate injection (EO) with meglumine amidotrizoate injection. For the stability evaluation of EOMA and EO, tests were performed with the samples prepared under 4 different conditions to observe changes in appearance with time, pH, oleic acid content, iodine value, benzyl alcohol content and amidotrizoic acid content for 8 weeks.
No abnormality was observed in appearance of all the samples of EOMA and EO, except slight development of a brown color in sterilized samples of both injections. Almost no change was observed in pH of both EOMA and EO during the 8-week test period. The pH of EOMA was lower than that of EO, since EOMA contained meglumine amidotrizoate injection of pH of about 6.5. No major change was observed in oleic acid contents and iodine values of both EOMA. and EO during the test period, nor was seen any difference in those values amongsamples prepared under different conditions, and benzyl alcohol also showed simila r results. Also amidotrizoic acid mixed in EOMA showed almost no change throughout the 8 weeks.
These results suggest that both EOMA and EO, prepared in any condition, are stable for 8 weeks, if they are preserved in a dark and cold place.

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Some powders become electrostatic during the process of packed filling and readily adhere to the filling eguipment. This causes the contamination of the other powder drug which is subsequently filled by the same equipment due to difficulty in complete cleaning of the equipment. In order to prevent te adhesion of drugs to the equipment, effects of various excipients against electrification of drugs were investigated. There was no excipient which decreases electrification of any drug. It is, therefore, necessary to find out an appropriate inhibitor for each drug and to determine its optimal concentration.
Pharmacists are required to operate packaging machine carefully in order to avoid the contamination of drugs and, at the same time, drug manufacturers are much expected to provide drugs free from being electrified.

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To estimate pharmacokinetic parameters for individualized theophylline therapy, a method available to clinical practice was studied in 2 healthy volunteers and 4 patients with bronchial asthma. At the beginning of the theophylline therapy (oral administration of aminophylline tablets 3 times daily), 2/3 of the daily dose of aminophylline was administered as a priming dose and 8 blood samples were taken for 12 hours, then residual 1/3 of the dose was administered. On the second day, a routine theophylline therapy was started, and 2 additional blood samples were taken to estimate parameters more accur ately.
The ability to predict serum theophylline concentration (STC) of the method based on repetitive dosing data was compared with that based on single-dose data. There was a statistically significant correlation between observed STC, (STC) obs, and that predicted, (STC) pre, by both method, however, prediction error ((STC) pre-(STCY obs)/(STC) obs) was smaller by the method based on repetitive dosing data (ranging from-14.5 to+26.4%) than by the method based on single-dose data (from-27.9 to+48.1%). The method based on repetitive dosing data can be used in clinical practice, because approximately accurate parameters can be estimated without interrupting, a routine theophylline therapy and with a little number of blood sampling.

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5-Fluorouracil (5-Fu) emulsion was prepared for the local treatment of uterine cancer. Sample emulsion was prepared by vigorous mixing of water, olive oil and surfactants (HCO-60, CMC-Na); the stability of various emulsions were examined. The results of stability test showed that stable emulsion could be obtained by mixing 30% of water and 0.3% or more of HCO-60. When CMC-Na was added at the rate not less than 0.01%, the stability of the emulsion was increased. The formula' of 5-Fu emulsion was selected on the basis of the results. Then 5-Fu emulsion was prepared according to the formula and infused into the uterine cavity of a patient with uterine cancer. Under the microscopic observation, 5-Fu emulsion proved to be present 8 hours after infusion, suggesting that it provides a good retention.

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