Pharmaceutical Technology - May 2019

Pharmaceutical Technology - eBook

Issue link: https://www.e-digitaleditions.com/i/1118782

Contents of this Issue

Navigation

Page 20 of 50

Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 21 cal emission spectrometry (ICP–OES), and inductively coupled plasma–mass spectrometry (ICP–MS). In these methods, organic solvents such as xylenes, toluene, and others are used to dissolve and separate the silicone oil from any inorganic silica. The objectives of this study were to: • Evaluate an ICP–OES method for the analysis of leachable silicone oil amounts in simulated bio- pharmaceutical formulations • Quantify silicone oil in typical pharmaceutical formulations (5) and evaluate the impact of com- monly used ingredients on the amount of leach- able silicone oil. In this study, an ICP–OES method was developed to quantify the amount of leachable silicone oil. Leachable silicone oil in aqueous biopharmaceutical formulations was extracted with an organic solvent, either with liq- uid-liquid extraction or solid-phase extraction, and the organic solution was analyzed directly with ICP–OES. Method performance such as method sensitivity, lin- earity, non-interference, relative response factors of dif- ferent grades of silicone oil, and method accuracy were evaluated. The study was followed by an evaluation of the leachable silicone oil amount in various simulated bio- pharmaceutical formulations stored in silicone-coated pre-fillable syringes. Formulations of simple phosphate buffers—and those containing co-solvents, bulking agents, chelating agents, and surfactants—and with dif- ferent pH levels were added to the pre-fillable syringes and stored at 5 °C, 25 °C, and 40 °C for a period of time and then analyzed for leachable silicone oil amounts. The impact of pH, co-solvent, surfactant, chelating agent, and bulking agents as well as storage temperatures on the amount of leachable silicone oil were investigated. Surfactant was found to be the most important factor affecting the amount of leachable silicone oil. Co-solvent, pH, and temperature also affected leachable silicone oil amount, while bulking agents, chelating agents, and buffer did not have a significant impact on the leach- able silicone oil amount. Overall leachable silicone oil represented a small portion of the coated silicone oil. Up to 2.1 μg/mL or 4.2 μg/syringe of leachable silicone oil was observed, which represented less than 2% of the total coated silicone oil. The study design Silicone-oil coated pre-fillable syringes (Becton Dick- inson) were used for the test system for this study. The total amount of silicone oil coating the inside of the pre-fillable syringes was determined by extracting the syringes with xylenes, followed by analyzing the extrac- tion solution by ICP–OES. Xylenes is a strong solvent for silicone oil and extracts out all coated silicone oil in the pre-fillable syringes. The amount of silicone oil in the pre-fillable syringes was determined to be 302 μg/ syringe. The standard used for quantitation was a silicone oil (Sigma Aldrich) with a viscosity of 350 cSt and 100% purity. The simulated biopharmaceutical formulations se- lected for the study included simple phosphate buffers with varying concentrations of propylene glycol (co- solvent), polysorbate 80 (surfactant), ethylenediami- netetraacetic acid (EDTA) (chelating agent), various sugars (bulking agents), and sodium chloride. A total of 15 different formulations were used in this study, as summarized in Table I. The solutions of simulated biopharmaceutical for- mulations were added to the pre-fillable syringes, 2 mL per syringe, and the syringes were then stored in chambers at 5 °C, 25 °C, and 40 °C. The syringes were pulled from the chambers after 30 days, and the con- tents were transferred to silicone oil-free glass contain-

Articles in this issue

Archives of this issue

view archives of Pharmaceutical Technology - May 2019 - Pharmaceutical Technology - eBook