The effect of bile salts and solvents on dissolution rate of phenytoin (PHT) from PHTpolyvinylpyrrolidone (PVP)-bile salts (1: 1: 1) solid dispersion (SD) prepared by a solvent removal method was investigated. Three kinds of bile salts, sodium deoxycholate, sodium cholate, and sodium lithocholate (LC-Na) were used. Methanol, ethanol, and n-propanol were employed as solvents. The dissolution rate of PHT from the PHT-PVP-LC-Na SD prepared with methanol was markedly increased among various SDs. Further, both X-ray diffraction measurement and infrared analysis were employed to confirm the estimation of the degree of PHT crystallization and for the characterization of interactions between PHT and additives such as PVP and/or bile salts as well.
Infrared spectra suggested an interaction, probably by hydrogen-bond formation, among PHT, PVP, and bile salts in SD. X-ray diffraction pattern of the powder indicated that PHT was amorphous in the PHT-PVP-LC-Na SD when methanol was used as a solvent. It was also revealed that the amorphous state of PHT in the SD attributed to the improvement of PHT dissolution property.

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An application to controlled drug delivery was investigated for dextran derivatives, a natural α-1, 6 glucan, in reference to the polyelectrolyte complex (PEC) formation between [2-(diethylamino) ethyl] dextran hydrochloride (EA) and sodium carboxymethyldextran (CMD). Compressed tablets containing theophylline (TH) as a model drug and dextran derivatives as fillers were examined.
PEC formation was examined by turbidity measurement and Fourier-transform infrared spectroscopy. A rapid dissolution of TH was observed when the tablet was prepared with lactose excipient. A controlled release of TH was observed in 1st and 2nd disintegration test fluid when the tablet was prepared with either physical mixture of EA and CMD or PEC consisting of EA and CMD as excipients. By applying the release date to Higuchi's equation, mode of drug release appeared to be not diffusion-controlled.

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Drug informations on a suitable insertion duration of suppositories and on a deal with the problem of the loss from rectal are essential for the proper therapy of patients. In the present study, we collected the data on drug disposition after administration of commercially available suppositories which had systemic pharmacological effects, and then analized pharmacokinetically on the problems of the insertion duration of them and the loss from rectal. The rectal absorption rate and the cumulative absorption ratio of drugs from commercially available suppositories were estimated by the deconvolution analysis. The plasma concentration data after rectal and intravenous administration were obtained in nine kinds of drugs, which were ampicilline, ketoprophene, indomethacine, acetoaminophene, phenobarbital, donperidone, bromazepam, buprenorphine and morphine. It was shown that the completion time of the absorption of drug from the suppositories varied largely from 50 min for ampicilline to 8 hours for donperidone. Comparing the time periods required to reach to 50% in the cumulative absorption ratio in those drugs, the fastest time was found in ampicilline (15 min), and the slowest was in aminophylline (90 min). These findings make it possible to the persue counseling for the patients on the proper insertion duration of each suppositories. The simulation of the time course of blood drug concentration after the loss of suppositories from rectal and the supplement of them was successfully performed, suggesting that the optimal drug concentration could be controled by the rational supplemental dose. In conclusion, the drug information based on the deconvolution analysis can be useful to instruct a rational use of suppositories to the pharmacist and/ or the patients.

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New time-effect curve (TEC) of antibiotics to compare antibacterial activity is proposed. It consists of a comparison of MIC with drug concentration in blood. A drug concentration at a certain time is obtained from time-concentration curve (TCC), and the expecting effect of antibacterial activity is obtained from MIC-cumulative percent of strain inhibited curves.
Antibiotics such as CCL or CPDX-PR show different TECs against each bacteria. Different TECs were obtained using only MIC when comparing with IPM/CS, CPZ and CFS. In the case of DKB, the speed of dropping injections was examined. Against E. coli, different shape of TEC was obtained for each dropping speed, but against P. aeruginosa and Staphylococcus, almost the same TECs were obtained. The dropping speed might not be so important in the latters.

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Mixing of azunol, xylocain and oradol gargle (OAKG) resulted in the formation of the precipitate which was characterized as the salt of azulene sulfonic acid and domiphen based on its IR and ^1-H-NMR spectrum. The concentration of sodium azulene sulfonate (SAS) and domiphen bromide in the preparation of OAKG is reduced by forming precipitates.

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It is supposed that the potentiation of an antiepileptic action which is clinically found by using phenytoin with both Shousaiko-to (T-9) and Keishikashakuyaku-to (T-60) (: T-9+ 60) might have to be caused by the change of pharmacokinetics of phenytoin. In order to estimate the effect of Kampo extracts, the influence on the pharmacokinetic parameters of phenytoin at 7 days after the oral administration of these three Kampo extracts of T-9, T-60 and T-9+60 was studied in rabbits.
In the treatment-groups of T-9 and T-9+60, the values of serum total (Ct) and free (Cf) phenytoin concentrations and half-life (T1/2) decreased. Total serum clearance (Cl) of phenytoin increased, and Cf/Ct and volume of distribution of phenytoin did not change. However, in the treatment-groups of T-60, all the pharmacokinetic parameters of phenytoin estimated did not produce any significant changes. These results suggest that the decrement of serum phenytoin concentration induced by the treatment with T-9+60 might mainly be due to the stimulation of hepatic phenytoin-oxidizing metabolic enzyme activity by T-9. The potentiation of the antiepileptic effect induced by the combination therapy of phenytoin and T-9+60 would not result in the increment of serum phenytoin concentration, but an independent pharmacological effect of phenytoin and T-9+60.

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A sustained release nifedipine fine granules, Sepamit R Granules^® (SP-RG), is a product prepared by using the technique of solid dispersion. Dissolution behavior of nifedipine from SP-RG was tested based on the results of incompatibility. The photostability of SP-RG was also tested. Dissolution rate of nifedipine from SP-RG was 12.5% in JP XII 1st disintegration test fluid (pH 1.2) and 100.9% in JP XII 2nd disintegration test fluid (pH 6.8). Dissolution of nifedipine in JP XII 2nd fluid was delayed by moisture absorption during storage (relative humidity of 75% at 20° for 30 days). Dissolution of nifedipine from SP-RG in JP XII 1st fluid was increased by mixing of SP-RG with sodium bicarbonate or heavy magnesium oxide during storage (relative humidity of 75% at 20° for 30 days).
Nifedipine in SP-RG packaged with polyethylene cellophan laminate paper completely decomposed after 72 hours, under exposure to light (500 lux), while it was stable even after 30 days with aluminium polyethylene laminate paper.

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Potential adverse effects in combinations of multiple drug usage are well known, and have been available on each product information. However, it has not been well established how to combine these informations useful in the process of routine prescriptions. In order to overcome these difficulties, a system using a personal computer and a commercially available data base program (dBXL) is developed. Using the system, the prescriptions of 1, 511 inpatients in the 2 wards served for the department of internal medicine in our hospital were analyzed. The survey was done during a period of June 1991 to May 1992, including 6929 dififferent drugs.
Of these prescriptions, 16.5% were found potentially hazardous due to drug interactions, except anti-tuberculosis agents. The highest 4 drugs prescribed with potential adverse interactions were anti-tuberculosis drugs, diuretics, anti-calcium antagonists and hypoglycemic drugs, respectively. Fortunately, none of these patients encountered with serious results of drug interactions. However, the results clearly indicate the necessity of a routine check system for potentially hazardous prescriptions with multiple drug usage. This simple and inexpensive system developed will be useful until a complete ordering system becomes available.

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Group education for patients has been performed at some medical institutions within the framework of team medicine. Until now, however, the role of pharmacists in team medicine has not been considered. We recently conducted a questionnaire survey involving 370 nationwide institutions. The questionnaire included questions primarily pertaining to group education for diabetic patients. This survey was aimed at examining:(1) diseases for which team medicine has been practiced, (2) the degree of pharmacists' involvement in team medicine, (3) future plans of pharmacists to engage in team medicine, and (4) views about team medicine.
This survey revealed that group education for diabetic patients was performed in 75% of the institutions examined. However, pharmacists were involved as teaching staff in only 39% of the institutions conducting such classes. The survey additionally disclosed that group education, within the framework of team medicine, was performed for more than 20 diseases in addition to diabetes mellitus. Forty-eight percent of all respondents affirmed the necessity of participation in educational team of patients. Some institutions replied that pharmacists can not participate in team medicine because of a shortage of pharmacists. However, the number of prescriptions handled by a pharmacist did not differ significantly between the institutions where pharmacists were involved in group education for diabetic patients and the institutions where they did not. Therefore, it is elucidated whether or not pharmacists should be involved in team medicine depend on the attitude of the pharmacy department.

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In order to obtain the pharmaceutical information on the compatibility of mitomycin C ophthalmic solutions, we investigated the stability test for prepared eye drops and the sensory test for eye drop resolvent of mitomycin C by 5 volunteers (pharmacists). Six kinds of mitomycin C ophthalmic solutions, 0.04% mitomycin C in 5% glucose solution, isotonic sodium chloride solution, water for injection, artificial tear solution, Palitzsch buffer (pH8.0) and phosphate buffer (pH8.0) which were used postoperative instillation in the treatment of primary pterygium were used for stability test, and we observed the change in appearance, pH, osmotic pressure, and quantitatively analysed mitomycin C at regular intervals. When stored at room temperature or 5°C, in the Palitzsch buffer (pH8.0) or phosphate buffer (pH8.0), mitomycin C was comparatively stable, while in 5% glucose solution, the change was observed after 2 weeks and the concentrations of mitomycin C were reduced to 69.0%, 85.4% respectively. The stability of mitomycin C was influenced by the pH of the solutions, the degradation constant (k) of mitomycin C at 30°C was pH8.0< pH7.0< pH9.0< pH6.0< pH5.0.
From the results of sensory test, all the 5 volunteers felt obvious stimulations in eyes by water for injection.

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Compatibility tests of lysozyme chloride ointment (Reflap^® ointment) with anti-skin ulcer agents, steroidal agents, anti-microbial agents, nonsteroidal anti-inflammatory agents, vitamin agents and disinfectant were carried out. Reflap^® ointment was mixed with isodine sugar ointment and U-pasta ^® by weight of 1: 1 and 3: 1 and mixed with the other ointments and creams in equal weight. And a day's dose of anti-microbial injections and 5ml disinfectant solution were, respectively, mixed with 30g Reflap ^® ointment. The mixtures in polyethylene airtight vessels were stored at room temperature for two months. Changes of appearance (e.g., color, odor and bleeding), pH level and lysozyme activity were studied.
It was found that the brown oil phase was slightly separated and lysozyme activity was decreased in the mixture with isodine sugar ointment and U-pasta ^® in equal weight. The color of the mixture with minomycin ^® injection was changed from slightly yellow to yellowish-brown, but lysozyme activity was not changed. In cases of the mixture with Eulax^®, Sahne^® ointment and Juvela ^® ointment, the significant reductions of lysozyme activity immediately occured. No changes were observed in any of other mixtures.

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Eight kinds of the filter units were chosen to investigate the presence of UV absorbing substances in filtrate. In all of them, these substances were observed. Especially, in filter units which contain nitrocellulose membrane filter, nitrate was detected by qualitative reaction and determined by high-performance liquid chromatographic method.

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Stability of aspirin in 2% aspirin ointment was studied using micellar electrokinetic chromatography (MEKC) which is one of the methods of capillary electrophoresis.
The preparation of a sample is very simple, only to disperse a few milligrams of ointment into a buffer by ultrasonication.
A half life of aspirin in 2% washable aspirin ointment at 30° was found to be 51.7 days determined by MEKC, which corresponds to the value obtained by HPLC.

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University Medical Information Network (UMIN) has been developed by connecting all of the national university hospital host computers. Through this network, hospital personnel share in the benefits of various medical information services. We attempted to send/receive MSDOS drug information system files by UMIN. UMIN does not accept binary data, but the “ish file converter” has enabled us to convert binary data files to text files for uploading and downloading. New ADMICS (Advanced Drug Mixture Information & Consultation System) has been developed on FMR (Fujitsu) personal computers by investigating ADMICS files on PC-9800 (NEC) personal computers. A batch file made it possible to update ADMICS automatically and immediately with files downloaded from UMIN. UMIN is expected to facilitate collaboration among university hospitals in utilizing application programs and databases originally developed on MS-DOS at each university hospital.

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In recent years, considerable attention has been focused on the subject of drug-drug interactions and the extensive drug informations concerning to these occurrences have been widely provided to health care professionals by many ways and means. However, there are few previous studies in the concrete guidelines for the prescribers to avoid significant harmful drug-drug interactions, the understanding of the guidelines by the prescribers, and the effects of the guidelines on the drug therapeutic regimens.
In this study, we issued a booklet for the drug information about new quinolones-metal cations interactions, which contained informations about how to avoid this drug-drug interactions. We also provided this booklet to all prescribers in our hospital by direct mail, and then we analyzed the effects of the booklet on the therapeutic alteration when the pharmacists detected this drug combinations in the prescriptions and recommended how to avoid the interaction. After the booklet was provided to the prescribers, the prescriptions with both drugs dramatically decreased and remained on a stable level. Furthermore, the 93% of the prescriptions containing both drugs are changed appropriately based on our recommendations. It is suggested that such information is very useful educational program for the health care professionals. In future, in order to support the rational drug therapeutic regimens by the prescribers, it is necessary to introduce the prescription checking system to the hospital.

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