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1.
J Pharm Sci ; 88(4): 454-8, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10187757

ABSTRACT

Intravenous lipid emulsions are used for total parenteral nutrition and as carriers for lipophilic drugs. Exposure to the high temperature (121 degrees C) required for steam sterilization may cause coalescence and an increase in droplet size. The purpose of this study was to investigate whether an increase in the electrostatic repulsive force between oil droplets produced by formulation modification improves the thermal stability of lipid emulsions during autoclaving. The addition of a small amount, 0.66 or 1.32 mmol/kg (mm), of purified anionic phospholipid fractions (phosphatidic acid, phosphatidylglycerol, or phosphatidylinositol) to the standard formula increased the zeta potential from its normal value of -11 mV to -39 mV. Emulsions with the larger negative zeta potential did not exhibit any change in oil droplet size or distribution during steam sterilization at 121 degrees C for 15 min. The autoclaved emulsions having the larger negative zeta potential did not exhibit any evidence of coalescence when samples were stored for 1 month at 4 degrees C, room temperature, or 40 degrees C. Reduction of the negative surface charge of the oil droplets by the addition of stearylamine confirmed that the surface charge was an important factor, as emulsions having a reduced negative surface charge separated into two phases during autoclaving.


Subject(s)
Emulsions/chemistry , Drug Stability , Drug Storage , Electrochemistry , Fatty Acids, Nonesterified/chemistry , Hydrogen-Ion Concentration , Phospholipids/chemistry , Sterilization , Surface Properties , Temperature , Triglycerides/chemistry
2.
Pharm Dev Technol ; 2(1): 81-6, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9552433

ABSTRACT

The purpose of this study was to stabilize the phosphate adsorptive capacity of aqueous suspensions of ferrihydrite, a potential phosphate binder. Ferrihydrite was precipitated by the addition of 1 N NaOH to 1 M FeCl3 until pH 8.0 was reached. The ferrihydrite suspension was divided into three portions and an amount of sorbitol was added to produce sorbitol concentrations of 0, 1, or 5% w/v, respectively. The phosphate adsorptive capacity and X-ray diffraction pattern were periodically determined during aging at room temperature. The phosphate adsorptive capacity of the ferrihydrite suspension containing 0% sorbitol decreased steadily from 0.012 mgP/mg to 0.007 mgP/mg during the 1-year aging period. In contrast, suspensions containing 1 or 5% sorbitol exhibited constant phosphate adsorptive capacities during this period. X-ray diffraction patterns revealed that ferrihydrite transformed to hematite and goethite during aging of the control suspension. The presence of 1 or 5% sorbitol prevented the transformation of ferrihydrite to more crystalline iron oxides. This study suggests that the phosphate adsorptive capacity of ferrihydrite suspensions can be stabilized by the incorporation of small amounts of sorbitol into the formulation.


Subject(s)
Ferritins/chemistry , Phosphates/chemistry , Sorbitol/chemistry , Adsorption , Chemistry, Pharmaceutical , Crystallization , Drug Stability , Ferric Compounds , Suspensions , Thermodynamics , X-Ray Diffraction
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