Osmotic Activity of Drugs is an Important Factor of Their Local Action at the Injection Site: What We Don't Use to Prevent Post-Injection Abscesses

Abstract

It is established that very few modern high-quality drugs in the dosage form "Solution for injection" have isoosmotic activity in the range of 280-300 mosmol/l of water. The main part of solutions for injection is hypotonic or hypertonic solutions, which can have osmotic activity in the range of 0 - 4000 mosmol/l of water. The reason for this was that the osmotic activity of drugs is not included in the list of controlled indicators of drugs quality, so it is not subject to control. It is shown that the osmotic activity of drug solutions increases with an increase in the total concentration of all dissolved ingredients present in the solution. It was found that an excessively high concentration of the drug in the solution gives it an excessively large hyperosmotic activity, which can cause a local irritant and cauterizing effect at the injection sites due to dehydration of the cells. Therefore, to exclude post-injection abscesses, it is proposed to dilute the hypertonic drug with water for injection until it is given isotonic activity.

Post-injection Complications. Nicolau Syndrome as a Consequence of Local Irritant Effects of Drugs, Including Antiseptics, Local Anesthetics, NSAIDs, Steroids and Anticoagulants

“…However, in recent years, the cause of postinjection inflammation, necrosis and abscess has finally been established. It has been shown that the cause of Nicolau syndrome is a very strong local irritating effect of medicinal solutions [26]. This became possible because the local irritating effect of drugs on tissues at injection sites is not controlled, as it is not included in the standard of drug quality control [27].…”

“…It has been shown that in addition to this, the standard for quality control of medicines does not include an assessment of their osmotic activity [28]. In addition, it has been shown that the drug quality control standard allows for the presence of high acidic or high alkaline activity in some medicinal solutions [26][27][28]. It is reported that drug solutions considered to be of high quality today may have isotonic and weak alkaline activity, but sometimes (in some serial numbers or in some pharmaceutical companies) drugs by chance (by ignorance) may have hypotonic or hypertonic activity, high acid or alkaline activity, as well as a strong local irritant effect, which in some cases, it can transform into a cauterizing effect [26].…”

“…In addition, it has been shown that the drug quality control standard allows for the presence of high acidic or high alkaline activity in some medicinal solutions [26][27][28]. It is reported that drug solutions considered to be of high quality today may have isotonic and weak alkaline activity, but sometimes (in some serial numbers or in some pharmaceutical companies) drugs by chance (by ignorance) may have hypotonic or hypertonic activity, high acid or alkaline activity, as well as a strong local irritant effect, which in some cases, it can transform into a cauterizing effect [26]. In experiments on pigs, it was shown that dilution of medicinal solutions several times with water for injection to impart isotonic activity completely prevents the development of Nicolau syndrome with subcutaneous injections [28,29].…”

“…The discovery of this cause for the development of post-injection complications became possible use of information about the manufacturer of the drug (pharmaceutical company), the date of manufacture of the drug, the batch number, the formulation of the drug, physical-chemical indicators of the quality of the drug solution, in particular, the concentration of all ingredients, the pH value and osmotic activity of the drug solution [26][27][28].…”

“…It is reported that the standard of quality control of drugs does not include control of osmotic activity, as well as local dehydrating and irritating effects of drugs [26]. Therefore, some injection solutions that are currently considered highquality may not have isotonic activity.…”