The effects of the degree of mixing (coefficients of variation, C. V.) and the error of divided weight (C. V.) on the error of divided components (C. V.) were investigated with 84 formulations combining 4 different powder preparations and 7 different diluents of fine granular preparations. Target components of the powder preparations were labeled with ^113mIn. The relation between the error of divided component (Y) and the sum (X) of the degree of mixing and error of divided weight was expressed as follows: Y=0.80+0.81 X, r=0.88.

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In order to obtain stable oral emulsion of 5-fluorouracil (5-FU) dry syrup, kind of surfactants and the ratio of their combination, as well as the method of preparation of the emulsion and its physical stability were studied. In the study, a method of preparation was established: Sesame oil and surfactants (HCO-60, MGS-B: HLB=10.4) were dissolved in oil phase, and 5-FU dry syrup in water phase. Then, 2 phases were, heated to 700 and the emulsion (o/w type) was obtained by ultrasonic vibrations. Anti bacterial effect of the 5-FU emulsion was studied. The potency was not reduced even after storage for 30 days. The emulsion was comparatively stable when stored at room temperature. In the study of tissue distribution, the AUC level of 5-FU in the lymph node of mice after oral administration of the emulsion was higher than the concentration after administration of 5-FU dry syrup solution. The 5-FU emulsion showed excellent lymphotrophic effect, thus proving that it is clinically very useful.

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The acid-resistance of 2 kinds of tablets (A and B) and 3 kinds of capsules (C, D and E) containing enteric-coated granules was compared. Alkaline protease activity dissolved from samples was measured in different test solutions:(a) pH 5.0, 6.5 and 7.5 test solutions, (b) lst fluid and 2nd fluid in disintegration test (J. P. IX), and (c) pH shift test solution in consideration of pH values of gastrointestinal tract. The following results were obtained:(1) At pH 5.0, 4 of the 5 samples (except C) did not disintegrated after 120 min, and at pH 6.5 only sample B scarcely disintegrated. At pH 7.5, the disintegration times of tablets tested were 2-3 times longer than those of the enteric-coated granules.(2) Entericcoated granules in sample C met disintegration test (J. P. IX), butthe enzyme activity in 2nd fluid was 30% weaker than that at the optimal pH.(3) For the pH shift test solution, enzyme activities of samples A, B and E rapidly increased 180 min after start of the test, when pH of dissolution medium exceeded 6.0. Maximum activities of these three samples were slightly weaker than those at the optimal pH, and the activityof sample C decreased 70%. Digestive potential of the samples estimated from the area under activity curve according to Berndt method was compared with each other. The acid-resistance of samples A, B and E was better than C, indicating that digestive potentials of the three preparations were higher. The digestive potential was very useful for evaluationof the acid-resistance of enteric-coated film.

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The insolubilized antibody-enzyme immunoassay technique (MARKIT method) was compared to absorptiometry and homogeneous enzyme immunoassay technique (EMIT method) for determining phenytoin, phenobarbital and primidone in plasma. There was good agreement between results of MARKIT method and absorptiometry, and between MARKIT method and EMIT method.
MARKIT method was also applied in determination of concentrations of these drugs in plasma water and mixed saliva. MARKIT method is useful for determining low concentrations of antiepileptic drugs in plasma water and mixed saliva.

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Stability of dibekacin sulfate in the ointment prepared with use of macrogol ointment, white petrolatum and hydrophilic ointment as base was examined in changes in external appearance and potency. Results are summarized as follows: 1) Change in appearance: The ointment prepared from dibekacin sulfate kneaded with macrogol ointment became moist and liquified with time when stored at 25° and relatative humidity 93%. Mixture of dibekacin sulfate with white petrolatum changed color from light yellow to yellowish brown on exposure to light, and the mixture with hydrophilic ointment became light yellow on the surface. 2) Potency: The potency of dibekacin sulfate, mixed with any of the 3 ointment bases, lowered by about 10 to 15% when irradiated with light for 3 months. The lowering of potency could not be prevented by antioxidant tocopherol. Dibekacin sulfate was almost stable under other conditions of temperature and humidity.

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To evaluate quality of 3 brands of capsules (A, B and C) and 2 brands of tablets (D and E) of seaprose S, weight variation test, content test and dissolution test were made. All products met weight variation test of capsule or tablet (J. P. IX). In the content test, mean content percentage of products B and C were about 82% of each labeled amount and those of the remaining 3 products were not less than 90%. To test acid resistance of the enteric-coated films of each product, activity of seaprose S dissolved in the 1st fluid and the 2nd fluid of disintegration test (J. P. IX) were determined. It was found that the acid resistance of the enteric-coated granules of products A and B was insufficient; especially, the activity of product A dissolved in the 2nd fluid decreased to a half of the activity recorded in the content test. Then, to find the cause of the decrease in activity, protein content and activity of seaprose S dissolved in both fluids were measured simultaneously. It is suggested that seaprose S in granules was partially deactivated by permeation of the 1st fluid through the enteric-coated films and, after that, seaprose S was slowly dissolved in the test fluids. Maximum activities of products A and B in pH shift test solution were 20 and 30%, respectively, of those recorded in the content test. It is, as a result, considered that products D and E are satisfactory enteric-coated preparations.

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The factors which cause death of the living cells in a bifidobacterial preparation (Lac B) were studied. When the relative humidity exceeded 50%, or when the moisture absorption in the preparation exceeded 5%, the number of the living cells rapidly reduced at 27°. In such humidity, however, death of the cells was not observed during 10 days, when the temperature was maintainedat 4°. When the cells, dried over P2os, were compounded with the same quantity of a dried drug and stored under dry condition, the number of living cells did not reduced for 1 week even at 37°.

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Poly-glassine paper for Konishi's packaging machine and polyethylene film for Pile Packer's packaging machine, Merix-Packer, were examined for their property of protectingthe bifidobacterial preparation (Lac B) from moisture. When the preparation was kept at 27°and at relative humidity 79%, the living cells of the preparation in the poly-glassine paper disappeared at the 5th day, and those in the polyethylene film at about the 10th day. Then, methods of storage with use of these papers were examined. The number of living cells did not reduce for at least 2 weeks when stored at 4°in an electric refrigerator or at room temperature in a metal can containing blue silica gel.

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Fluidizing phenomena of powders and granules are roughly divided into gravity fluidity and forced fluidity. The former occurs by the particles' own weight and the latter by external force. Behavior of mixtures of powders and granules of different physical properties was studied in terms of vibration fluidity (one of the forced fluidity) with use of a linear vibrating feeder.(The study must be significant in view of the recent development of automatic powder packaging machines.) Separation phenomenon was not so remarkable at the vibration acceleration 520 cm/sec² in the following combinations: granule+granule, fine granule+fine granule, granule+fine granule, and fine granule+powder. The separation was marked in the combination of granule+powder, disregarding the variation of vibration acceleration. The best distance between hopper and feeder was found to be 3 mm. Behavior of powders and granules in different particle size were measured at different vibration acceleration. The behavior on vibrating feeder may be affected by property of powders and granules, types and materials of feeder and hopper, and other factors. Therefore, these factors should be studied.

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On the basis of the questionnaires sent back from 426 institutions, we investigated the actual conditions and moot points of the equipments for dispensing. Powder packing machine has spread to 98.6% of total institutions surveyed, and it has become indispensable for hospital pharmacies. Compared with the results of the study previously made in 1969, both the rate and number of the institutions installed with the equipment have increased, and the efficiency of the device has been improved. Recently, automatic dividing and packing machine has been used very widely. The rate of institutions having tablet crushers for dispensing remained as low as 60.1%, and that of those having mixers for diespensing was far lower, 37.1%. One-dose packaging was practiced, in various ways, at 67.4% of institutions. Drug dust clearing system was installed at 55.2%, and 2/3 of the institutions reported that the system helped prevent pharmacy allergy. Most of the non-installed hospitals desired to have such system.

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Dividing weight error of powders with an automatic medicine dividing and packing machine (Konishi 727-K10 type) was investigated at the slit gap M (ca. 2.5 mm) and the middle intensity of vibration. When the machine's starting position of effluence of 2g crystalline lactose in 1 package at 21 or 30 divisions was changed, dividing weight error indicated coefficient of varition (C. V.) 4.3-8.8%. The starting position which minimized the dividing weight error was found to be 17 th hole in case of 21 divisions and 20 th hole in case of 30 divisions. Dividing weight of the first 2 packages and the last 2 packages at the turn was significantly lighter than that of other packages. In case of 30 divisions, C. V. of error in dividing weight of 0.5g crystalline lactose in 1 package was about 17%, that of 1. 0g 10%, 2.0g 4%, 3.0 and 4.0g 6%. Dividing weight error of several powders with different physical properties in 2g package at 30 divisions was investigated. C. V. of crystalline lactose was 4.3%, that of lactose fine granule 5.7%, corn starch 9.5%, and synthetic aluminum silicate 13.6%. Powdered lactose was indivisible.

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