In January 2005 Federal Service on Surveillance in Healthcare and Social Development of Russian Federation (RZN) pinned Russian pharmaceutical companies down to go on to the production of pharmaceuticals, including water for injections and parenterals, in accordance with the GMP standards that is achieved by double-distillation technology. Currently the requirements of Pharmacopeial Item FS 42-2620-97 amendment 1 “Water for Injection” are obligatory for all pharmacy productions. In fact the main method to obtain water for injections in pharmacies is monodistillation. Meanwhile, there is information that this method does not fully ensure the water quality according to FS.
It is known that BE (in other words aggregates of lipopolysaccharides) are negatively charged in a faintly acid, alkaline and neutral medium due to phosphate groups of glycosidic residues. This property is used for their removal by sorption on positively charged sorbents, for example, ion-exchange resins.
In this work, positively charged polyamide membranes MMPA+ were used as the sorbents. An investigation was performed in order to establish the possibility of producing distilled water (mono-distillation) of pharmacopoeial quality, excluding the energy-intensive process of repeated distillation. Distilled water was filtered through the samples of polyamide membrane for several days until the membrane resource was exhausted. Pressure differential was held constant of 0.015 MPa. The determination of BE concentration in water was performed before and after filtration. Water samples were examined for BE in the Laboratory of Pharmacology, FSC "Scientific Center for Evaluation of Medical Products" of RZN.
The test results are presented in the table below.
BE concentration in the distilled water after filtration through polyamide membranes
|Sample Characteristics||The quantity of filtered water, % of total throughput||The concentration of BE, EE / ml|
|Initial distilled water||-||0,166-0,196|
|Filtrate after MMPA+ - 0.2||34,3||Less than 0.01|
|Filtrate after MMPA+ - 0.2||85,0||0,0174 - 0,0195|
|Filtrate after MMPA+ - 0.45||0,5||Less than 0.01|
|Filtrate after MMPA+ - 0.45||60||Less than 0.01|
As follows from the table, all membranes performed satisfactorily, keeping the level of BE in distilled water lower or barely reaching the "alarm level" of 0.03 EE / ml (EE-endotoxin unit) up to 84-86% of the total throughput for membranes MMPA+ - 0.2 and below the "alarm level" for 60% of the MMPA+ -0.45 throughput.
Recommendations for filter cartridges
The obtained results can be treated as the basis for performing experimental developments for obtaining "water for injections" from mono-distilled water, using capsules with a positively charged polyamide membrane with brand name KFM.K+ produced by Technofilter LLC.