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28 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 P h a r mTe c h . c o m Analytics enhance the low aqueous solubility of silicone oil for these formulations. Leachable silicone oil for formulations with co-solvent. The leachable silicone oil analysis results for the formula- tions with propylene glycol as a co-solvent are sum- marized in Table VIII. The data indicated there was detectable leachable silicone oil in all the formulations with propylene gly- col as a co-solvent, but the overall leachable silicone oil amounts were low, even with 10% propylene glycol in the formulation. The amount of leachable silicone oil in the formulations after 30 days stored in the syringes at 5 °C, 25 °C, and 40 °C was still below 1 μg/mL, or below 2 μg/syringe. Considering there is more than 300 μg silicone oil coated on each syringe, only a very small portion of the coated silicone oil (less than 1%) leached into the formulations. The primary reason for this is the low solubility of silicone oil in water. The addition of the co-solvent propylene glycol only slightly enhanced the solubility of silicone oil for these formulations. Leachable silicone for formulations with surfactant. The leachable silicone oil analysis results for the formula- tions with polysorbate 80 as surfactant are summa- rized in Table IX. The data indicated there was detectable leachable silicone oil in all the formulations with polysorbate 80 as a surfactant in the formulations. The amount of leachable silicone oil ranged from 0.2 μg/mL to ap- proximately 2.0 μg/mL. The amounts of leachable sili- cone oil were more than those observed for all other formulations, including formulations with propylene glycol as a co-solvent, suggesting that among all the typical ingredients in the biopharmaceutical formula- tions, surfactant is the most significant ingredient that may enhance the silicone oil solubility in the formula- tion and thus cause more leaching of silicone oil. Storage temperature affected the leachable sili- cone oil amounts, with the greatest leachable sili- cone oil amounts typically observed at 40 °C com- pared to 5 °C and 25 °C storage. The greatest leachable silicone oil amount observed in formulations with polysorbate 80 as surfactant in this study was approximately 2 μg/mL, which is equiv- alent to 4 μg/syringe. Considering there was more than 300 μg silicone oil coated on each syringe, the leach- able silicone represented less than 2% of the coated sili- cone oil. This means only a very small portion of the coated silicone oil leached into the formulations, even for those with surfactants. Leachable silicone for formulations with different pH. The evaluation of pH impact on the leachable silicone oil amounts was performed with formulations with poly- sorbate 80 as a surfactant because the formulations Table V. Recovery of spiked silicone oil in formulation with no polysorbate 80. Method performance evaluation- recovery test with formulation: 20mM phosphate, pH 6.8, 7% sucrose, 150mM NaCl, 0.1mM EDTA. Replicates Recovery % 1 92% 2 93% 3 93% Table VI. Recovery of spiked silicone oil in formulation with polysorbate 80. Recovery test with formulation: 20mM phosphate, pH 6.8, 7% sucrose, 150mM NaCl, 0.5mM EDTA, 1% polysorbate 80. Preparation Replicates Recovery with Liquid/ Liquid Extraction Procedures Recovery with Solid Phase Extraction Procedures 1 49 94 2 43 117 3 49 118 Table VII. Leachable silicone oil in formulations without co-solvent or surfactants. Formulations 5 °C 25 °C 40 °C 1 (phosphate buffer) 0 0 0 6 0 0 0 7 0 0 0 14 0 0 0 15 0 0 0