Stability of cefapirin sodium (CEPR), a cephalosporin antibiotic, in 15 different infusion solutions and in an aqueous solution was studied with high-pressure liquid chromatography. It was found that the compound was quite stable in the infusion solutions for 6 hours at room temperature, and may be feasible for regular drip infusion. Des CEPR or CEPR lactone with low anti-bacterial activity was produced as CEPR degraded in solutions at pH 10 or 2.

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The Bioavailability of digoxin in the commercial tablet and powder was compared. At first, the concentrations of digoxin in plasma and saliva of 5 healthy volunteers were determined by radioimmunoassay following oral administration of digoxin. The bioavailability of the tablet was found to be higher than that of the powder. Secondly, the dissolution rates of digoxin in tablet and powder dissolved in 1st fluid (J. P. IX) at 37° were measured according to U. S. P. XIX. Then, the tablet was found to have a higher dissolution rate than the powder. Therefore, the rate of absorption is considered to be correlated with the dissolution rate. The salivary digoxin measurement may be expected to be a monitoring factor since the digoxin concentration in saliva is correlated with that in plasma.

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The acid-resistance of enteric coated films and the dissolution pattern of Futraful enteric coated granules were monitored with the U. S.P. dissolution tester in various pH test solutions: a) pH 1.2, 5.0, 6.0, 6.5, and 7.5 test solutions, and b) pH shift test solution in consideration of gastrointestinal coated films were found to show satisfactory acid-resistance in the test solutions at pH 1.2 and 5.0, because the rate of dissolution measured 120 min after the onset of the test was less than 10%. In the pH 6.0 solution. the time required to achieve 100% dissolution rate was 140 min after the onset of the test, whereas the times for the 100% dissolution rate in the pH 6.5 and pH 7.5 test solutions were 50 and 10 min, respectively. For the pH shift solution, the rate of dissolution increased gradually in the first 280 min, and then the rate increased rapidly, when pH of dissolution medium exceeded 6.4. Therefore, the rate of dissolution was slightly low.

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Rectal suppositories of digoxin were prepared from cacao butter containing 5 % of polysorbate 60 and 1, 2, or 5 % of sucrose fatty acid esters with HLB value of approximately 11 and 15 (SFAE-11, SFAE-15). Physical properties such as melting point, dissolution time and hardness of these suppositories were determind. Blood samples of rabbits were collected at 0.5, 1.5, 3.0, 4.5, 7.0 and 9.0 hours after rectal administration of digoxin (0. 3mg/kg). The plasma digoxin levels were determined by a radioimmunoassay method. Long lasting effect for digoxin suppositories containing SFAE-11 and SFAE-15 was estimated from the relative areas under the concentration-time curve over 0 to 9 hours, and the ratios between 0.5 hour value and 1.5 hour value of plasma digoxin concentration-time curve for digoxin suppositories containing 1, 2, or 5 % of SFAE-15 were 1.52, 2.14 and 2.23, respectively. The ratios for the suppositories containing 1, 2, or 5 % of SFAE-11, as determined by Formula 1 as standard, were 0.67, 0.87, and 1.23, respectively. The ratios between 0.5 hour value for Formula 1 to 7 was 0.55, 0.54, 0.70, 0.89, 0.77, 0.91, and 0.94, respectively.

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The concentrations of phenytoin, phenobarbital and prlmidone in plasma and saliva were determined. The result obtained by MARKIT method showed a good agreement with that by EMIT method, with the exception of the determination of low concentration of phenytoin in saliva. However, when the phenytoin concentration in plasma was above 2.0μg/ ml, it was possible to determine salivary phenytoin in low concentration by adding one of the following operations to EMIT method: 1) concentration determined by CP 1000 and then calculated from the half-dose standard curve of DPH-calibrators diluted by DPH negative human serum; 2) concentration determined by CP 5000 in similar test method of plasma sample. In both operations, the salivary dilution omitted from EMIT method.

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Temperature of large volume liquid in respective containers (1-3l) was continuously measured with thermocouple under autoclaving in order to determine the time for the temperature of the liquid to reach 115°. Sterilization temperature, regardless of a number of containers per load, was uniform even at various locations of the containers in the chamber. In spite of rapid rising and lowering of temperature, exhausting time was so long that the ingredients were decomposed. The size of containers was the most important factor in raising liquid temperature to 115°; 40 min for the 3l container. The degree of sterilization was estimated from Log Inactivating Factor (LIF) based on a first-order reaction and the course of temperature under autoclaving. LIF was very useful for the determination of sterilization time, because it considerably agreed with a number of surviving B. stearothermophilus. The sterilization time of the 3l container was thus determined at 60 min corresponding to LIF 11.

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Interactions of Futraful with IVH maintenance solution were investigated. The maximum rate of decomposition of Futraful in the solution was as low as 4%, indicating that the compound was not affected by any of ingredients present in IVH. Though column size and solvents system were taken into consideration according to Wills' method, water-soluble vitamins were decomposed in IVH, but not affected by Futraful.

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Compatibility of MY-101 fine granules (50%) (Alclofenac, anti-inflammatory and analgesic agent) was investigated in terms of change in appearance and residual activity measured with UV spectrophotometry and iodometry. The mixtures of clinically expected combination with each of 61 different preparations were placed in a weighing bottle without top and wrapped in polyethlene-laminated cellophane paper or pile packer film, where the mixtures were observed under relative humidity (RH) of 75% at 25°, or 52% at 5°. As a result, the incompatibility was found in 15 preparations at RH 75% and 25°, and only Migrenine at RH 52% and 5°.

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Incompatibility of clindamycin palmitate hydrochloride dry syrup (CLDM-P·EHCl-DS) in various internal solutions was studied. Above pH 4.1, hydrochloride was dissociated from clindamycin palmitate, and a white turbidity was produced. CLDM-P·HCl-DS was dissolved in 14 different solutions, where 10 gave a change in appearance. When stored below 5°, CLDM-P·EHCl-DS solution often turned to a white gel.

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