The mefenamic acid (MFA)-casein solid dispersions were prepared for the purpose of enhancing the dissolution properties of MFA by two different methods, lyophilization and solvent evaporation.
In the case of the solid dispersions prepared by the lyophilization method, the X-ray diffraction patterns indicated that MFA in the solid dispersion lost its crystalline property. But diffraction peaks still remained in the solid dispersion prepared by the solvent evaporation method.The dissolution rate of solid dispersions prepared by lyophilization method markedly increased, and the solid dispersion at 1: 3 w/w mixing ratio of MFA to casein gave the maximum amount of dissolution which was three times as much as that of MFA alone.It was suggested that supersaturation of MFA in dissolution medium was caused by the crystalline inhibitory effect of the casein.
In the case of the solid dispersions prepared by the lyophilization method, the X-ray diffraction patterns indicated that MFA in the solid dispersion lost its crystalline property. But diffraction peaks still remained in the solid dispersion prepared by the solvent evaporation method.The dissolution rate of solid dispersions prepared by lyophilization method markedly increased, and the solid dispersion at 1: 3 w/w mixing ratio of MFA to casein gave the maximum amount of dissolution which was three times as much as that of MFA alone.It was suggested that supersaturation of MFA in dissolution medium was caused by the crystalline inhibitory effect of the casein.

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The significance of the position of nonflat punch on dividing prcperties of scored tablets was investigated in several tablets prepared from excipients or granules by one side compaction method.For the excipients, lactose, perfiller^®and microcrystalline cellulose were used.For the granules, sieved granules in 12-16, 16-32 and 32-48 mesh incorporating either hydroxy propyl cellulose or potato starch as binder was used.
Different influence of the position of nonflat punch on dividing strength of scored tablets was observed between the case of excipients and granules.Dividing strength of scored tablets made from excipients was not affected by the position of nonflat punch.But tablets made from granules had a tendency to show high dividing strength when tablets were compressed by nonflat upper punch.Then weight variation of divided tablets showed a tendency to become less when compressed by nonflat upper punch in both tablets made from excipients and granules.It was suggested that the effect of the position of nonflat punch on dividing properties of scored tablets was caused by different pressure lines during tablet compression.

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Analysis of fasting effect on biperiden distribution in rats was examined.The plasma concentration at 24 hr after i.v.injection of 3.2mg/kg varied between 0.45ng/ml (10-week-old fasted rats) and 1.4ng/ml (10-week-old normal rats).The steady state distribution volume of biperiden in the fasted rats was smaller by 2/3 than that in the normal rats.The determined percentage of fat tissue per body weight reduced from 7.6 to 2.3% was caused by fasting. There was a good correlation between the steady state distribution volume of biperiden per lean mass body weight and the fat volume per lean mass body weight (r=0.989) in four different groups (10-week-old fasted, 4-, 10-, and 50-week-old normal rats).The fat/plasma concentration ratios at 8 hr after the i.v.injection varied between 380 (10-week-old normal rats) and 550 (10-week-old fasted rats), whereas the brain/plasma concentration ratios were identical to those at steady state among the two groups.The time courses of biperiden concentration in plasma, brain, and fat were simulated using a physiological pharmacokinetic model.There was reasonable agreement between the model predictions and the observed data, suggesting that the change in the fat volume is a dominant determinant of the distribution volume of biperiden in rats.Changes in fasted tissue and plasma concentrations are discussed in relation to the clinical usefulness of the blood level monitoring.

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Effects of chlorpromazine (CPZ) on serum GPT (SGPT) and hepatic microsomal drug-metabolizing enzyme activities in the rat with liver injured by CCl₄ were studied.Rats were intraperitoneally injected with CCl₄ at a dose of 0.2ml/kg every 3 days, and with CPZ at a dose of 5 mg/kg once a day for 48 days. SGPT activity was gradually elevated from the beginning of CCl₄-administration and reached to the maximum after 30 days.The elevation of SGPT value induced by CCl₄-administration was inhibited by the administration of CPZ.In addition, decreases of cytochrome P-450 and cytochrome b₅ by CCl₄-administration were observed.However, CPZ restored the decrease of cytochrome P-450.These results indicate that CPZ protects liver cell damage induced by CCl₄, resulting in that the effect of CPZ on cytochrome P-450 may be important for protecting from drug-induced hepatic injury.

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For the topical treatment of rheumatalgia arthritis, four kinds of 2% aspirin washable ointments using crotamiton (formula 1), crotamiton with 2% anhydrous sodium sulfate (formula 3), crotamiton with 5% anhydrous sodium sulfate (formula 4) and isopropanol (formula 2) as solubilizers, respectively, were prepared. Stability of aspirin in aspirin ointments (4 kinds) was examined by HPLC with UV detection. Aspirin in any ointments was stable for 21 days at 5°C, but unstable at 20°C and 30°C. Among 4 formulas, formula 1 gave the best results on the sensory tests.
Five patients with rheumatalgia arthritis were treated with the 2% aspirin ointment (formula 1). The pain of the patients was relieved moderately or markedly. The pain started to fade within 5-15 minutes and the pain relief usually lasted for 1-8 hours after treatment.With respect to the pain relief, the ointment (formula 1) was the most effective as compared with the indometacin ointment and cataplasm (cold type). From these results, 2% aspirin ointment (formula 1) appeared to be an effective analgesic for the pain associated with rheumatalgia arthritis.

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Non-steroidal antiinflammatory drug (NSAID) challenge tests were given to patient with aspirin-induced asthma (AIA) to observe the changes of the forced expiratory volume in one second (FEV_1.0) between before and after challenges.PL granules for children (PL®) as acid NSAID, that consists of 45 mg salicylamide, 25mg acetaminophen and 10 mg anhydrous caffein per gram, mepirizole and tiaramide hydrochloride as basic NSAID, and syoseiryuto as chinese traditional medicine were used.FENT_1.0 was measured before and several times after oral challenges of NSAIDs and syoseiryuto, and decrease of more than 20% of the initial value (basal value) was defined as a positive response.
PL, Acid NSAID, showed clear positive response 30 min after challenge, but basic NSAID mepirizole and chinese traditional medicine syoseiryuto showed negative response.On the other hand, tiaramide hydrochloride, that is also basic NSAID, showed positive response when administered 40 mg although negative in a dose of 20 mg.These results suggest that the administration of NSAID to patient with AIA, even in a case of basic NSAID, must be done carefully, and it should be carried out as challenge tests in those cases.

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Azathioprine injection was prepared as an immunosuppressive dosage form for organ transplantation. The stability of azathioprine in the injection was investigated under various sterilization and storage conditions.The amount of azathioprine was determined by highperformance liquid chromatography.The amount of azathioprine in the injection decreased slightly after autoclaving but any significant difference was not observed among three sterilization conditions such as 115°C for 30 min, 121°C for 20 min and 126°C for 15 min.Azathioprine in the injection which was autoclaved at 115°C for 30 min was completely stable under subsequent storage at room temperature on exposure to light for 4 weeks.The present azathioprine injection was found to be useful as an immunosuppressive agent for organ transplantation.

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The Frequency of the simultaneous use of Kampo drugs and other drugs was investigated on out-patients' prescriptions at Tohoku university hospital from March 1 to 31, 1989.Kampo drugs were administrated for many disease. But there were a few docters who had given Kampo drugs following Kampo diagnosis.Kampo drugs were used for the following diseases; “ Shosaiko-to” -chronic hepatitis; “Gosya-jinki-gan” -diabetes, “Sairei-to” -nephrosis.On an avarage 3.8 drugs were simultanously prescribed with a Kampo drugs per one prescription. The principal examples of the simultaneous use of drugs are as follows; “Shosaiko-to” -glycyrrhizin; “Gosya-jinki-gan” -vitamin B₁₂;Kampo drugs for chronic obstructive pulmonary diseases-β-stimulant;Kampo drugs containing Glycyrrhizae Radix-diuretic drugs and so on.
The simultanous use of Kanpo drugs themselves (Gappo) comprised 8.0% of Kampo prescriptions. Some of the constitutional crude drugs such as Glycyrrhizae Radix, Ephedrae Herba and Aconiti Tuber were overlapped.It was suggested that it is important to inspect Kampo prescriptions in the pharmacy.

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The frequency of the simultanous use of Kampo drugs was investigated on out-patients' prescriptions at Tohoku university hospital from March to April, 1990.The simultanous use of Kampo drugs themselves (Gappo) comprised 8.6% of Kampo prescriptions. Some of the constitutional crude drugs were overlapped as Grycyrrhizae Radix, Ginseng Radix, Rehmanniae Radix and Ephdrae Herba.
The Kampo prescriptions were inspected by considering the following two points. 1. Similar Kampo drugs like Saiko drugs, 2. Kampo drugs with the same origins.Consequently, about 10% of Gappo fell under each category. It was concluded that it is important to inspect Gappo in the pharmacy.

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A formulating system of instruction for drug administration has been introduced and applied to student education.This manual includes 29 common basic diseases.Each manual for each disease consists of two parts, namely, a summary of the disease and guidelines for the medical use of the drug.Standardized descriptions and references to prepare the manual were presented. It was suggested that such manuals were useful not only in educating patients, but also in educating students for the process of their preparation.

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We investigated the stability of vitamins in hyperalimentation fluids adding trace minerals. Test samples were prepared by adding trace minerals to three kinds of hyperalimentation different dextrose/electrocyte concentrations.The time-course of the potencies of vitamins and pH of the test samples with and without trace minerals were determined under three different conditions as follows: room temperature with shield or exposure of light and cold dark place. Total vitamin C content including oxidized dehydroascorbic acid was determined, and these results showed that the residual rate of the total vitamin C was decresed with the addition of trace minerals under room temperature with shield of light.The effect of the addition of trace minerals was also noted markely in the test samples under cold dark place.On the other hand, we observed no direct effect on stabilities of vitamin B₁, B₂, B₆, folic acid, A, E, and K₁, by adding trace minerals.

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Grinding of tablets and opening of filled capsules are often requested as a part of dispensing. Current status of grinding of tablets was investigated on out-patient and in-patient prescriptions in Kumamoto University Hospital in April, 1990.It was shown that the frequency of prescriptions ordering grinding of tablets was about 2% of total prescriptions.Weight loss in tablet contents caused by grinding process was investigated with seven kinds of plain tablets, namely prednisolone, Halcion^®, Thyradine^®-S, Cortril^®, quinidine sulfate, Androcur^®, and Baktar^®.Two methods of grinding, one using a mortar and pestle and the other using a tablet grinding machine, were compared.
In both methods the extent of loss in weight varied with numbers of tablets and with weight of each tablet employed.The increase in loss in weight was attended by the decrease in number of tablets and weight of each tablet.The loss in weight by the method using a tablet grinding machine was decreased by adding lactose (crystalline type).

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The clinical advantage of fluorescence polarization immunoassay for determination of cyclosporine (CYA) based on monoclonal antibody (M-FPIA) was compared with high-performance liquid chromatography (HPLC), radio immunoassay on monoclonal antibody (M-RIA), and fluorescence polarization immunoassay on polyclonal antibodies (P-FPIA).To clarify the evaluation of this method (M-FPIA), whole blood levels of CYA in 24 renal transplant recipients, who were treated by CYA therapy, were determined by each analytical method.
The coefficients of variation obtained by M-FPIA for the within-run and between-run precisions were 2.1 to 2.5% and 1.5 to 3.2%, respectively.There was a significantly good correlation between the data of HPLC and those of M-FPIA (r=0.988), M-RIA and M-FPIA (0.988), P-FPIA and M-FPIA (0.942), however, the value of CYA by P-FPIA was 2-fold of the value of the drug by M-FPIA.The values with M-FPIA were approximately the same as those with HPLC and M-RIA.These results suggest that M-FPIA be very useful for the emergent and routine monitoring of CYA on the clinical practice.

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