Satoshi Nishii

Delayed neurotoxicity produced by an organophosphorous compound (Sumithion)

A case of late-onset manifestation of organophosphorous insecticide poisoning is described. The patient was a 70-year-old female who ingested 40ml Sumithion emulsion (50% fenitrothion). At first, no toxic symptoms were apparent. However, 48 h after ingestion certain signs became apparent. An impediment in consciousness was observed. Fasciculation and muscular weakness were noted, while plasma and urinary 4-nitro-3-methylphenol (NMC), the degradation product of Sumithion, reached a maximum. Neither atropine sulfate nor PAM (pyridine 2-aldoxime methiodine) were effective. For 3 weeks the patient required ventilatory support, and consequently her muscle strength and neurological status gradually recovered with falling NMC levels.

Pharmaceutical evaluation of change of phenytoin dosage form from powder to fine granule.

Phenytoin (PHT) fine granule, which has the same bioavailability as the tablet, has recently been marketed. We projected a change of PHT dosage form from usual powder to fine granule. In view of the fact that 97% of PHT products prescribed and marketed are available in fine granules, 50% PHT preparations were produced in hospital pharmacy. 5 kinds of preparations using various lactoses as diluents were prepared and tested for their quality. Among them, the preparation from Aleviatin fine granule passing through a 42-mesh sieve and EFC lactose showed the best results in the mixing property and various sense tests. The change to this dosage form and its bioavailability tests were carried out by a cooperation of doctors and pharmacists. Serum PHT levels of all patients, assayed by EMIT method, showed a 20% to 30% increase after the administration of the new preparation (50% PHT fine granule with EFC lactose).

Toxieity of Swallowed Micra-batteries

With recent advances in electric technology, about 300 million micro-batteries are manufactured annually in Japan, being widely used for childrens electric toys as well as for cameras, watches, calculators, and hearing aids. The accidents of ingestion of the batteries by small children have often been reported in the past one year. These batteries consist of an outer nickel-plated container (cathode) and a cap (anode) which are jointed by a plastic seal. They usually contain highly concentrated potassium hydroxide, mercury salts, zinc and some others depending on the type.This paper describes the process of corrosion and leakage of the batteries in several kinds of solutions. It also analyzes the 11 cases of inadvertent ingestion of the batteries which our poison informatiqn services accepted in the last half year.

Screening Test of Microbiological Status of Solutions for Internal Use and of Radiopaque Media by the Method Described in PAB Notification No.297

The microbial quality control of 41 solutions or suspensions for internal use and of 8 radiopaque media was investigated by the test method described in PAB Notification No.297 (valid on April 1, 1976). All of the 49 pharmaceutical products tested met the standard requirements provided in the Notification, so that they are considered to be under good microbial quality control. Most of the sample solutions of radiopaque media were turbid and were difficult to be put to the test for microbial count. In this point, the test method for the microbial count is desired to be improved. A test method of estimating the possible antimicrobial activity of products is also desired to be standardized, because the antimicrobial activity may affect the final results of the tests in the Notification.

Evaluation of Microbial Contamination of Pharmaceutical Products

Twenty one pharmaceutical products which had shown a positive reaction of microbial contamination in all of the 5 culture media in the previous sterility test were selected for this test. This paper compares the levels of microbial contamination in the latest test with those in the previous test conducted 3 years before, and also analyzes the tendency of the recent quality control of pharmaceutical products in relation to microbial contamination. In the latest study, total aerobic microbial count of more than 10000/g was observed in 3 of the 21 products, showing the same incidence as in the previous test. Total aerobic microbial count of less than 1, 000/g was observed in 15 products, as compared to 10in the previous test. Coliform organisms were detected in 2 products, compered to 6 in the preceding study.

Quality Test of Timed-Release Form of Iron Preparations

A test method to check the dissolution pattern of timed-release preparations is described. Rotation method of U. S. P. XIX was used as a dissolution tester. First, 900ml of dissolution medium containing 2.0ml of diluted HCl and 2.0g of NaCl in 1000ml was used. By exchanging 5 ml each of the medium with the same volume of the second solution (disintegration, J. P. IX) at the intervals of 10 min for the first 1hr and of 15 min for the subsequent 4 hrs, pH of the medium was designed to change gradually from 2.3 to 3.5 in the first 150 min, rapidly from 3.5 to 5.7 in the following 30 min, and gradually up to 6.5 after 300 min, volume of the medium being kept at a fixed level. The rotation rate of basket was 100 rpm. Under the above condition, dissolution curves of iron preparations in 5 dosage forms of different manufacturers were compared. Maximum dissolution percentage varied from 27 to 92% among samples. At about pH 4, precipitates were formed in the medium as a result of the decrease of solubility of iron into the medium. The rates of dissolution of 6 dosage forms in the same lot number in the first 120 min varied largely, from 5 to 20%.

Spectrophotometric Assay of Nitrazepam in Commercial Tablets

The stability of nitrazepam was studied in three different solutions for the assay of the drug. Nitrazepam in the ethanol solution was very stable and showed a linear standard curve at the maximum absorbance of 310 nm. In the first solution (disintegration test, J. P. IX), the ultraviolet (UV) absorption spectrum changed with time. However, no change in absorbance was observed at 252 nm and a linear standard curve was given at this wavelength. In the second solution (J. P. IX), the UV absorption spectrum showed no change.For the assay of nitrazepam in commercial tablets, the first solution, instead of ethanol, is preferable as extraction solvent because of its better extraction effect of nitrazepam from tablet; the wavelength of 252 nm is more precise than the maximum wavelength at about 280 nm for the spectrophotometric asssay of the extracted solution.