Compatibility of sodium valproate (SV) fine granules with phenytoin, caffeine and sodium benzoate, acetylpheneturide, dried yeast, trimethadione or Cabagin-U^® was investigated by highperformance liquid chromatography.
Changes in compatibility were observed in the mixtures of SV with almost drugs except for Cabagin-U^® under the severe conditions (25°C, RH 75%).
These results, suggest that Cabagin-U^® is the suitable drug in mixing with SV.And then, since SV may be administered for as long as 30 days, caution should be exercised in mixing this drug with other agents.

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To evaluate the drug release from a suppository by the designed dialysis tubing apparatus, commercially available indomethacin and sodium diclofenac suppositories were used.A dialysis tubing, in which a suppository was put, was immersed in the release fluid maintained at 37.0±0.3°C, and the release amount of drug released across the dialysis tubing was determined.The release rate of both drugs across the dialysis tubing of 70Å of pore size was faster than that of 25Å of pore size.In the case of fatty base, the drug diffusion through the dialysis tubing was constant when the length of dialysis tubing contacting with the release fluid was more than 7.0cm.The suitable rotation speed in the release fluid was 50rpm considering small variation in the released amounts.The proposed dialysis tubing method should offer a useful means of measuring the drug release from suppository and the reproducibility of the release curves was acceptable.

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For the purpose of administration of aminophylline (AP) to pediatric patients with as much accuracy as possible, we attemped to prepare tablets containing a low concentration of AP. First, the effect of some additives on hardness, disintegration time and dissolution rates of the AP tablets were examined with various formula.Twenty-four kinds of tablets, containing various amounts of polyvinylpyrrolidone (PVP) and/or hydroxypropylcellulose (HPC) as binders, starch only or a mixture of starch with calcium diphosphate, dibasic as diluents, and carboxymethylcellulose as disintegrator were prepared following the wet granulation method.Tablets containing a 3% or higher concentration of binders met all of the requirements restricted by the JP XI.Tablets containing HPC and/or PVP had controlled dissolution rates.Although the disintegration time of these tablets decrease as the starch percentage increase, there appears to be a critical starch concentration level.
These results suggest AP tablets that closely resemble standard tablet in the dissolution profiles could be manufactured by adding various proportions of binders.Therefore, if a hospital changes half of a single available 100mg-AP tablet to 50mg-AP tablet, bioavailability may not be affected.

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Aminophylline (AP) is an important drug on bioavailability.Therefore, if a hospital changed half of a single available 100mg-AP tablet to 50mg-AP tablet, significant changes to bioavailability are undersirble.So two kinds of tablets, each containing 50mg of AP were prepared on the basis of their dissolution rates: tablet No.I containing HPC 4% and tablet No.II containing a mixture of HPC 2% with PVP 3% and evaluated both in vitro and in vivo.
These experimental tablets met all the requirements restricted by the JP XI.For the in vivo evaluation, Neophylline^®tablets were cut in half and used as a standard preparation.AUC values were calculated by the trapezoidal method.The AUC percentage of the experimental tablets to the standard preparation was found to be 95.54%for the No.I tablet and 91.90% for the No.II tablet.Thus, both of these AP tablets were bioequivalent to half of a single Neophylline^®tablet.
These results suggest that if AP tablet was changed from half of Neophylline^®tablet to 50mg AP manufactured in hospital, its bioavailability is not affected.Therefore, 50mg-AP tablets we developed could be clinically applicable for pediatric patients.

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Ofloxacin (OFLX) is one of the oral antibacterial agents belongs to pyridone carbonates.We assayed OFLX by high-performance liquid chromatography (HPLC) using the deproteinization with acetonitrile for pretreatment of serum.Mobile phase consisted of 40mM H₃PO₄ and 10mM KH₂PO₄ in 90% acetonitrile-water (pH 3.5).We used DL-8357 as an internal standard (I. S.) Serum (20μl) was taken in the polyethylene tube, and 200μl of the acetonitrile containing I.S. was added into the tube, and the tube was centrifuged for 1 min mixing.
After the centrifugation 25μl of the supernatant was injected into the HPLC.This method is a simple and required short time, and its producibility was good.

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The release rates of indomethacin from 5 kinds of commercially available suppositories were compared by using three different methods, i.e., dialysis cell, membrane diffusion, and cylindrical filter paper.The release from each fatty base by the method of membrane diffusion was about 30% for labeled amount after 120min, and that from each macrogol base was 23%.By dialysis cell method, indomethacin released from macrogol base was about 80% after 120min, whereas that from fatty base was 26-37%. The maximum plasma concentrations of indomethacin after rectal administration of both products A and B composed of macrogol base to rabbits was 31.8μg/ml, and those of products C, D, and E of fatty base were 21.4, 15.0, and 34.7μg/ml, respectively.The in vitro release rate was not concerned in the plasma concentration of indomethacin.It was found that the volume of suppository markedly influenced the rectal absorption, because correlation coefficient between the maximum plasma concentration of indomethacin and the volume of suppository was 0.932.

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The loss of cyclosporine from solutions into the intravenous delivery system was investigated. Concentration of cyclosporine was measured with high-performance liquid chromatography. When the cyclosporine solution was passed through the administration set 100cm in length at a flow rate 0.58 m1/min, and initial concentration 49.5μg/ml, the concentration of cyclosporine was reduced to about 86% in 15 min, and gradually returned to the initial level with time.
With the solutions stored in a glass or a polypropylene container no drug loss was observed but with a polyvinyl chloride bag the concentration of cyclosporine was reduced to 94.4%in 24 hr.It was found that the factors effecting on the loss of cyclosporine from intravenous solutions were the kind of containers, the length of the administration set, the concentration of cyclosporine injection and the flow rate of solutions.

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Inhibitory effects of various protease inhibitors on complement-hemolysis were investgated in vitro.In the hemolytic action system for classical pathway, sensitized sheep erythrocytes at a concentration of 2.0×10⁸ cells/0.2ml and diluted normal human serum were used, and in alternative pathway, unsensitized rabbit erythrocytes at a concentration of 1×10⁸ cells/0.4ml and diluted normal human serum were used.
Gabexate mesilate, camostat mesilate and nafamostat mesilate inhibited complement-hemolysis including both the classical and alternative pathways, but aprotinin and urinastatin did not inhibited at 100 fold concentration of usual dose.Among these protease inhibitors, nafamostat mesilate strongly inhibited complement-hemolysis.With usual dose, nafamostat mesilate obviously indicated anti-complement activity.

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Selenium injection for intravenous hyperalimentation was prepared and quality test was conducted on their content uniformity, pH, osmotic pressure, and pyrogen test.
For the determination of selenium in injection, an yellow selenium-Bismuthiol II complex formed in hydrochloric acid solution was extracted quantitatively with chloroform and washed the chloroform extract with a buffer solution (pH 7.5) to remove the excess reagent from the organic phase.The measurement of absorption of the organic phase at 334nm was applied for the determination of small amounts of selenium.The mole ratio of selenium to Bismuthiol was 1: 4 by means of continuous variation method.This method is considered to be highly suitable for routine analysis.
The standard contents of the element in the injections were determined in the range of 98 to 102%. The pH was decreased after the sterilization.Then, osmotic pressure of selenium injection was 2.20±0.45 mOsm/ml.All samples were negative to pyrogen test (Limulus Lysate).

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Anhydrous tetracaine-glycerin injection was prepared for the diagnostic block of cancer pain.In addition to this preparation, hydrous tetracaineglycerine injection was prepared for the treatment of herpetic pain or postherpetic neuralgia.The stability of these preparations was investigated under various sterilization and storage conditions.The clinical availability was also evaluated.Tetracaine in these preparations was completely stable under autoclaving and the subsequent storage at room temperature on exposure to light for 8 weeks.Anhydrous preparation was found to be useful as an agent for diagnostic block of cancer pain in all of 13 patients.All of 10 patients with herpetic pain gained a satisfactory relief of the pain following injection of the anhydrous or hydrous preparation, whereas the patients with postherpetic neuralgia gained no complete but temporary relief of pain.

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The frequencies of prescription and drug assay for routine therapeutic drug monitoring of antiepileptics were surveyed for a year from May, 1984 to April, 1985.This was the first year at which the routine therapeutic drug monitoring was started in our hospital.The results obtained were compared with those of more recent surveys.The antiepileptics examined were phenobarbital, phenytoin, carbamazepine, valproic acid, primidone, and ethosuximide.
The annual number of drug assays was 2, 617 for the first year and 2, 748 in the following year.More than 85% of the annual drug assays were from the clinic of pediatrics and more than 90% of the assay were from outpatients.The prescription frequency of these antiepileptics ((prescription number of the drugs/total prescription number) ×100) was examined in outpatients and the result was 6.21% for the first year.This showed similar value to 6.94% of February, 1987.The frequency of multiple antiepileptic medi: ations (more than three different drugs) was 11.06, 9.25, and 9.01% for the first year, the following year, and February, 1987, respectively.This shows improved prescription of the drugs, that is, multiple medications were replaced with monotherapy.Moreover, a good correlation between monthly prescription frequency and number of assays for the drugs was obtained (n=6, r=0.943, p<0.01).
Through these surveys, we might be able to discuss about the effects of therapeutic drug monitoring on antiepileptic medications.

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For the purpose of supply of intravenous hyperalimentation solutions (IVH) for home care, we examined long-term stability, especially vitamins B₁, B₂, C and A for two weeks to monitor changes in hospital coded prescription, IVH 1-5.
Decrease of vitamin B₁ was observed in IVH 1-4 with time.It was decreased by 27.0-40.5 % on the 14th day, while in IVH 5 the concentration decreased to at 83.7%.Vitamine C showed the next largest decrease to 65.1% being retained two weeks in IVH 5.In IVH 1-4, on the other hand, it remained at 83.6-94.4%.Other two vitamins B₂ and A remained stable at the comparatively high level of 80.9-101.4% in each preparation.
From the results, it is seemed that if the constituents of IVH are given sufficient consideration, it would be possible to guarantee the long-term stability of IVH with vitamins in the index of vitamins B₁ and C.

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