Formulation,Optimization, Characterization,and Pharmacokinetics of Progesterone Intravenous Lipid Emulsion for Traumatic Brain Injury Therapy |
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Authors: | Jin Zhao Quan Yuan WeiHui Cai Pan Sun LiYan Ding Fang Jin |
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Affiliation: | 1.Shanghai Engineering Research Center of Lipid Emulsions,Shanghai,People’s Republic of China;2.Shanghai FrontHealth Pharmaceutical Technology Co. Ltd,Shanghai,People’s Republic of China |
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Abstract: | Traumatic brain injury (TBI) is a major cause of mortality and disability throughout the world. Progesterone (PROG) plays an important role in neurologic treatment. The aim of this study was to develop a progesterone formulation with good physical and chemical stability. Progesterone intravenous lipid emulsion (PILE) was prepared based on one-factor-at-a-time experiments and orthogonal design. The optimal PILE was evaluated for mean particle size, particle size distribution, zeta potential, morphology, pH, osmolarity, entrapment efficiency, storage stability, and pharmacokinetics in ICR mice compared with the commercial progesterone products. The droplets of PILE had the smallest possible diameters of 218.0?±?1.8 nm and adequate zeta potential of ?41.1?±?0.9 mV. The volume percentage of droplets exceeding 5 μm (PFAT5) of PILE was 0.003?±?0.0015% and much less than the specified standard. The TEM imaging proved that emulsion droplets had a smooth spherical appearance. Chemically and physically stable PILE was obtained with excellent entrapment efficiency that was up to 95.23%, with suitable pH at 7.15?±?0.01 and osmolarity at 301.3?±?1.2 mOsmol/l. Storage stability tests indicated that the emulsion was stable long term under ambient temperature conditions. Animal studies demonstrated that the emulsion was more effective with the higher progesterone concentration in the brain compared with commercial products. Therefore, the optimized PILE would offer great promise as a means of progesterone delivery for TBI therapy. |
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