Chemical stability of oseltamivir in oral solutions.
The stability of oseltamivir in oral aqueous solutions containing the preservative sodium benzoate was studied by a stability indicating HPLC-method. The separation was achieved on a RP-18 ec column using a gradient of mobile phase A (aqueous solution of 50 mM ammonium acetate) and mobile phase B (60% (v/v) acetonitrile/40% (v/v) mobile phase A). The assay was subsequently validated according to the ICH guideline Q2(R1). The extemporaneously prepared "Oseltamivir Oral Solution 15 mg/ml for Adults or for Children" (NRF 31.2.) according to the German National Formulary ("Neues Rezeptur-Formularium") was stable for 84 days if stored under refrigeration. After storage at 25 degrees C the content of oseltamivir decreased to 98.4%. Considering the toxicological limit of 0.5% of the 5-acetylamino derivative (the so-called isomer I) the solution is stable for 46 days. Oseltamivir was less stable in a solution prepared with potable water instead of purified water. Due to an increasing pH the stability of this solution decreased to 14 days. Furthermore a white precipitate of mainly calcium phosphate was observed. The addition of 0.1% anhydrous citric acid avoided these problems and improved the stability of the solution prepared with potable water to 63 days. Sodium benzoate was stable in all oral solutions tested.
Albert
K
K
Control Laboratory of Deutscher Arzneimittel-Codex, Eschborn, Germany. albert@govi.de
Bockshorn
J
J
D000284:Administration, Oral; D000998:Antiviral Agents / Q000032:analysis / Q000737:chemistry*; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D053139:Oseltamivir / Q000032:analysis / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D011310:Preservatives, Pharmaceutical; D015203:Reproducibility of Results; D020160:Sodium Benzoate
D000998:Antiviral Agents; D019999:Pharmaceutical Solutions; D011310:Preservatives, Pharmaceutical; D053139:Oseltamivir; D020160:Sodium Benzoate