Mode of rectal absorption of aminophylline was examined with 3 kinds of suppository bases, macrogol, Vosco H-15, and Vosco S-55. Plasma concentration of theophylline after rectal and oral administration was also measured on the subjects of 5 healthy adults. Measurement was made by the high-pressure liquid chromatography.
Drug releasing test was made by the method of Kakemi et al. Physical property, melting point, dissolution time, and other properties of the suppository were measured. The drug releasing test demonstrated that the release of aminophylline from macrogol base was faster than that from Vosco bases (in vitro test). Plasma concentration of theophylline was found higher in the oleaginous base (Vosco) than in the water-soluble base (macrogol). This is contradictory to the finding in vitro test.
In the human experiment, the highest mean plasma concentration of theophylline, 1.29 μg/ml., was observed 1 hour after rectal administration. The highest plasma concentration by rectal administration was slightly lower than that by oral administration.

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Methods of sulpyrine and aminopyrine suppositories labeled with a short-lived isotope ^113mIn were studied. The distribution of ^113m In-sulpyrine in the mixture of ^113m In-sulpyrine and cacao butter at 40° showed a coefficient of variation (C. V.) at about 1% immediately after cessation of stirring, 4% 10 min. after and 31% 50 min. after. When the melting temperature of the mixture was raised, C. V. of ^113m In-sulpyrine rose. The distribution of ^113m In-aminopyrine was not changed with melting temperature and time, and C. V. was within 10% at various temperatures of the mixture.
When the mixture of the active ingredients and the bases was poured into the suppository mold, C. V. of the active ingrediets was large with ^113m In-sulpyrine suppositories and small with ^113m In-aminopyrine. Therefore, in the preparation of the sulpyrine suppositories, the mixture should be poured into a mold with stirring at the temperature not higher than 40°. In the preparation of the aminopyrine suppositories, homogene us products are available by pouring the mixture into a mold with stirrig at 40-50°.

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Microcrystalline sulpyrine labeled with ^113m Indium was used in the preparation of suppositories. The particles of ^113m In-sulpyrine, varying in size from 1-20 μm, were suspended in cacao butter by fusion at 40-60°. The final preparation contained 5% of the ^113m In-labeled particles in the cacao butter. In order to determine the uniformity of the particle suspension in the suppository, the suppository was sliced into 5 fractions of equal height along the long axis. Each fraction was then examined for uniformity.
Suppositories prepared in the plastic molds had wide variation in the uniformity of the suspended particles. The effect of fusion temperature between 40 and 60° and cooling at 4° on uniformity was examined. The greatest deviation was consistently observed at higher temperature. At 40°, for example, the deviation from the mean of the upper fraction was -6%, and of the bottom fraction +10%. At 60°, the variation of deviation increased to -16 and +31%, respectively. When fusion was effected at 40° followed by cooling at -20°, the coefficient of variation (C. V.) was 4.5%, as compared with 20% in the fusion at 60° and cooling at 4°. With the metal mold, fusion temperature between 40-60° followed by cooling at 4° gave similar results. In all instances C. V. of the particle distribution was smaller than that obtained under the optimal conditions for the plastic mold (<4.5%).Therefore, for the preparation of suppositories of microcrystalline sulpyrine in cacao butter, metal molds are better than plastic molds in yielding consistent products over a wide range of fusion and cooling temperature.

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Quality of 3 multiple digestive enzyme capsules (PA, ST, HO) were compared in terms of their digestive activities in the digestive organs where the enzymes are dissolved, as well as of weight variations and protease potency variations (20 capsules for each sample). In pharmaceutical quality, PA was most excellent, followed by ST and HO, in that order, but amilase of PA must be improved. ST was noted for its long-sustained digestive activity. HO had weak digestive activity except for acid protease activity, and its dose should he 2-4 times as high as that of PA or

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Four brands of nalidixic acid tablets, one product (WM) of original manufacturer and three me-too products of different manufacturers, were tested for their pharmaceutical properties in vitro. One product (WR) did not meet the requirement for disintegration test of J. P. IX, though other products disintegrated in 6-13 min. In the dissolution test by paddle method with J. P.'s 2nd fluid, 80% of the WR content was dissolved in 20 minutes, a little slower than other 3 products. In 0.01 N NaOH solution, dissolution behaviors of these products were not always same as in the 2nd fluid. Generally, these four products proved to have relatively good qualities in regard to weight, content, dissolution and stability.

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The potency of ampicillin is known to be reduced when mixed with glutathione. Halogen or sulfonic acid group is related to the detoxication mechanism of Tathion. In this study, mixtures were prepared first by dissolving Tathion in halogen -or sulfonic acid groupcontaining injections such as Allergin, Metilon and Adona.Then the effect of Viccillin for injection, an ampicillin preparation, added to the mixtures, was examined by bioassay and colorimetry. It was found that the potency of Viccillin is well preserved by adding Allergin, Metilon or Adona mixed with Tathion.

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Apparent incompatibility of Catapres Fine Granules (0.015% clonidine hydrochloride), a centrally acting antihypertensive agent, with 51 drugs often used in combination was tested. Catapres wrapped manually with powder paper and that wrapped mechanically with laminated glacin paper were not moistened under medium conditions (20°, RH 75%) by themselves. Under the worst conditions (30°, RH 92%), the product by mechanical wrapping showed a marked moistening tendency in 4 days and that by manual wrapping in 2 days. Upon mixing with each of the 51 drugs under medium conditions, moistening or coloring was observed on mechanically wrapped 3 drugs: Aspara K, Chondron and Diastase. Catapres by manual wrapping increased the moistening tendency when mixed with SM powder, Alumigel and calcium lactate. It was concluded that Catapres is stable under weather in Japan and suitable for dispensing in combination with most drugs.

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Incompatibility of hydralazine hydrochloride with 22 other drugs was studied under the medium conditions (20°, RH 75%) and the worst conditions (30°, RH 92%). Change in appearance was observed immediately after mixing and 1, 2, 4, 7, 10 and 14 days after. Two weeks after mixing, coloring, moistening and other changes were observed in 18 mixtures under the medium conditions and in 21 mixtures under the worst conditions. The marked changes that made unpracticable the use of the products occurred in 1 mixture under the medium conditions and in 14 mixtures under the worst conditions. On the 9 mixtures with marked changes, quantitaive determination of hydralazine was made 1, 2, 4, 7, 10 and 14 days after their mixing. Hydralazine content, as a result, reduced in 4 mixtures under the medium conditions and in all mixtures under the worst conditions. It should, therefore, be recommended that hydralazine preparations are not mixed with antacids before their administration.

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Two brands of hydralazine hydrochloride powders which were respectively manufactured by Company T and Company Y in different production method were mixed with various antacids, theophylline, and choline powder, and their change in appearance and content were studied. The result showed that the production method gives effect on compatibility of the powders. The coated product of Company Y showed no change in combination with most of antacids except swertia and sodium bicarbonate powder, theophylline, and choline powder, while the product of Company T showed considerable change. When mixed with antacids such as dried aluminum hydroxide gel, heavy magnesium oxide, synthetic aluminum silicate, sodium bicarbonate, swertia and sodium bicarbonate powder, and SM powder, hydralazine hydrochloride showed the residual rate of more than 90% in most cases although the change in appearance was obseved.

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Water vapor permeability of hard gelatin capsule films was studied with use of gelatin films prepared in the same method of manufacture of hard capsules. Based on the change in weight of capsule films in the water vapor permeability test, it was suggested that water vapor passes not only through capsule film but through the capsule film-silica gel barrier. The water vapor permeability coefficient rose in parallel with the increase in relative humidity (RH), especially around RH 70%. That may be caused by the change in structure or physical properties of the capsule films due to swelling. The contact of capsule films and silica gel did not significantly affect the permeability coefficient.

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