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For particulates forming as a result of precipitation in intravenous injections and those arising from injection devices,we examined their distribution in tissue distribution following intravenous administration.Barium sulfate was used as the particulate and 100% (w/v) suspensions of varying particle size (1.5,5.0,10.0μm) were prepared.Each test suspension was injected into the caudal vein of ICR mice in a single dose of 0.1 mL/10 g and wholebody radiography was performed.Each suspension was also injected into the internal jugular vein of Hartley guinea pigs in a single dose of 5 mL/kg and major organs were collected for radiographic examination.The experiments were model-like and barium sulfate was injected in large quantities.The whole-body radiography of the mice revealed the presence of barium sulfate in the lungs,heart,kidneys,liver and external carotid arteries and the radiography of the guinea pig organs showed that barium sulfate was present in the lungs,heart,coronary artery,kidneys and liver.There were no obvious differences in tissue distribution for the three different particle sizes.Our findings indicate that particulates of less than 10.0μm could possibly be distributed throughout the body by passing through the lungs after intravenous dosing.The Japanese Pharmacopoeia places no restriction on particle fineness of 10μm or less to prevent pulmonary embolism and the results of the present study indicate that it is essential to eliminate particles of such size through the incorporation of a final filter (0.22μm).

The purpose of this study is to clarify the presence of so much insoluble microparticles in the injections and to con- ˆrm the usefulness of thenallter for its removal. The test drugs used were Doyle1 g vial, Cefotax1 g vial, Minomy- cin100 mg vial, Omegacin0.3 g vial, Maxipime1 g vial, Rocephin1 g vial, Isovorin25 mg vial, Diamox500 mg vial and Fungizone50 mg vial. 1) An appropriate volume of physiological saline was poured into the test drug vial from the 500 ml physiological saline bag. 2) The dissolution of the preparation was checked. 3) That test drug solution was returned into the same 500 ml physiological saline bag. 4) 5 ml of test drug solution was extracted from the inside of the 500 ml physiological saline bag. 5) The number of insoluble microparticles in the each test drug solution at pre- and post-ˆltrations were counted by using a particle counter for the solution. Two results were shown as follows (microparti- cle size: 5 m mo r greater), (a) Doyle 1g (ASPC): The number of insoluble microparticles in pre- and post-ˆltrations of aD oyle1 g vial were 250± 45 and 0/5 ml, respectively (microparticle size:≦5 mm 1662/ 5m l, 5~10 mm: 238/ 5m l,> 10 mm: 11/ 5m l). (b) Diamox500 mg (acetazolamide): The number of insoluble microparticles in pre- and post-ˆltra- tions of Diamoxwere 158± 53 and 0.3± 0.47/5 ml, respectively (microparticle size:≦5 mm 4030/ 5m l, 5―10 mm: 144/ 5m l,>10 mm: 14/ 5m l). The presence of great numbers of insoluble microparticles in several injection prepara- tions was claried. Although the all test drugs used cleared the criteria of the number of insoluble microparticles of the Japanese Pharmacopoeia, it was suggested to be not suitable that great numbers of insoluble microparticles were ad- ministrated in the body ‰uid of patients, because a possibility to occlude capillaries and/or to injure the tissues by them was been thought. But we could remove them nearly completely by passing the solutions of drugs through an infusion ˆlter. Otherwise, in this examination, we found that so much insoluble microparticles derived from the disposable syringe (10 ml) were used for dissolving freeze-dried preparations routinely (microparticle size:≦5 mm 329/ 5m l, 5―10 mm: 125/ 5m l,>10 mm: 39/ 5m l). These results suggest that incorporation of anallter in the IV line is extremely necessary not only for the prevention of bacterial infections, but also for elimination of insoluble microparticles. Key words―microparticles; removal; filter; freeze-dried preparation; contamination

A study on the prevention of angialgia induced by the high osmotic pressure of Peripheral Parenteral Nutrition infusion: Influence on the infusion system using Tandem method.During peripheral parenteral nutrition (PPN) infusions, angialgia more frequently occures than during other types of peripheral infusion. This is probably caused by the low pH, infusion speed and high osmotic pressure of PPN. We hypothesized that we could prevent angialgia by attenuating the osmotic pressures during PPN infusion. We therefore attempted examinations using the Tandem method as follows; It was possible to control the osmotic pressure in the effuent solution by changing the joining method of these infusions, thus suggesting that the specific gravity of these infusions affected the osmotic pressure.Specifically, we connected a hypotonic infusions (e.q., Soldem-3 A) with a low specific gravity to a PPN infusion (e.q., Amicaliq) with a high specific gravity, and the osmotic pressure of the effluent solution was maintained at a high level during the first 15 min, but thereafter gradually decreased. On the other hand, We connected a PPN infusion to a hypotonic infusion, and thus were able to maintain a low and constant osmotic pressure in the effluent solution.These results suggest that the Tandem method is useful in preventing angialgia due to the high osmotic pressure of PPN infusion. PPN infusion should thus be connected to a hypotonic infusion that has a lower specific gravity than that of the PPN infusion.