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Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 27 oil from the aqueous formulations into xylene. Equal volumes of the aqueous formulation and xylene were mixed, and the xylene layer was analyzed directly. Silicone oil recovery from the formulation was evalu- ated using Formulation 6 (20mM phosphate, pH 6.8, 7% sucrose, 150mM sodium chloride [NaCl], 0.1mM EDTA). The recovery data are shown in Table V. The data indicated that with liquid-liquid extraction pro- cedures, leachable silicone oil can be recovered from the formulation matrixes and quantified. For formulations with surfactant polysorbate 80, the liquid-liquid back extraction generated severe emul- sions, which yielded low recovery of silicone oil. A different technique, solid-phase extraction, was used to transfer the leachable silicone oil for formulations with surfactant. Silicone oil recovery from the formu- lation was evaluated by using Formulation 11 (20mM phosphate, pH 6.8, 7% sucrose, 150mM NaCl, 0.5mM EDTA, 1% polysorbate 80), and the recovery data are shown in Table VI. The data indicated that with solid- phase extraction procedures, leachable silicone oil can be recovered from the formulation matrixes and quantified. Determining leachable silicone amounts Leachable silicone oil for formulations with no surfactant or co-solvent. The leachable silicone oil results for five for- mulations with no co-solvent or surfactants are sum- marized in Table VII. The five formulations included simple phosphate buffer and formulations containing chelating agent (EDTA), tonicity modifier (NaCl), and different bulking agents (sucrose, mannitol, or trehalose). The amount of leachable silicone oil for all five formula- tions stored at the three different temperatures (5 °C, 25 °C, and 40 °C) was below the detection limit of 0.1 μg/mL; no leachable silicone oil was detected after 30 days. The primary reason for this was the low solubility of silicone oil in water. The addition of the chelating agent EDTA, tonicity modifier NaCl, or bulking agents (sucrose, mannitol, and trehalose) did not significantly 4500 4000 3500 3000 2500 2000 1500 1000 500 0 0 5 10 15 Concentration ug/mL (S) IR 20 25 30 Figure 1. Correlation of inductively coupled plasma/optical emission spectrometry (ICP-OES) responses vs. silicone oil concentration. (S) IR is standardized intensity ratio. ALL FIGURES COURTESY OF THE AUTHORS.