Abstract
The State Pharmacopoeia of the Russian Federation, 14th edition states that implants are a sterile dosage form, and have to be tested for pyrogens. However, it does not provide details on how the test should be performed for this dosage form.The aim of the study was to develop a LAL test procedure for detection of bacterial endotoxins (BE) in implants, using the example of a goserelin product.Materials and methods: BE extraction from the implant surface into an aqueous medium was performed with subsequent BE detection in the extract by turbidimetric kinetic test. The implant was then dissolved in dimethyl sulfoxide, and the obtained goserelin solution was tested for BEs using the gel-clot test.Results: the analysis of the Russian and foreign pharmacopoeial approaches to pyrogenic substance detection in hormonal implants helped to develop two sample preparation procedures for determination of BE content (in the extract and the implant solution). It was demonstrated that the BE content in the water extract did not exceed 0.01 EU/mL and was less than 0.07 EU per implant. The BE content in the implant solution was less than 8.3 EU per 1 mg of goserelin, which is almost eleven-fold lower than the theoretically-derived limit.Conclusions: the authors developed two test procedures for BE detection in hormonal implants using the LAL test, which could be included in manufacturers’ product files. The first procedure involves testing of the water extract from the implant surface and establishes the BE limit of no more than 20 EU/product. The second procedure involves complete dissolution of the implant in dimethyl sulfoxide and establishes the limit of not more than 97.22 EU per 1 mg of goserelin.
Highlights
The State Pharmacopoeia of the Russian Federation, 14th edition states that implants are a sterile dosage form, and have to be tested for pyrogens
provide details on how the test should be performed for this dosage form
bacterial endotoxins (BE) extraction from the implant surface into an aqueous medium was performed with subsequent BE detection in the extract
Summary
Расчет допустимой концентрации БЭ в смыве выполняется с учетом установленной нормы БЭ (не более 20 ЕЭ/изделие), количества изделий и объема воды для приготовления смыва. Для подготовки смывов предлагается использовать воду для ЛАЛ-теста, подогретую до 37 °С. 2. Процедура экстракции бактериальных эндотоксинов с поверхности имплантата в водную среду. Для этого испытуемые образцы растворяют в органических растворителях, исходные растворы разбавляют водой для ЛАЛ-теста до концентрации, при которой не обнаруживаются мешающие факторы растворителя. Цель работы — разработать методику определения содержания бактериальных эндотоксинов с помощью ЛАЛ-теста в имплантатах на примере гормонального препарата с активным веществом гозерелин. Для достижения цели необходимо было установить и апробировать подходы к определению БЭ в исследуемом объекте, предложить методику предварительной подготовки образцов для последующего определения содержания БЭ с помощью гельтромб теста и турбидиметрического кинетического метода
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More From: The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products
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