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The experimental objective was to evaluate change in pH, Osmolarity upon change in concentration of Mannitol and Sodium acetate anhydrous at fixed concentration of Gemcitabine hydrochloride. So the experiment was designed by varying the concentrations of two excipients Mannitol and sodium acetate anhydrous. A model was generated using Quadratic modeling and CCF design with eight runs in design and three centre points. The innovator product/ reference list drug composition corresponds to 45.5408 mg/ml of Gemcitabine Hydrochloride equivalent to 40 mg/ml of Gemcitabine, 40.0 mg/ml of Mannitol and 2.5 mg/ml of Sodium Acetate anhydrous. The low and the high levels of each factor were specified in relation to the reference list drug composition. It was decided to vary Sodium Acetate anhydrous concentration from 0 to 2.5 mg/ml and Mannitol from 30 to 50 mg/ml keeping the concentration of Gemcitabine Hydrochloride constant. Then a standard experimental plan with eleven experiments was created. For each of the eleven experiments Osmolarity, pH of the solution was measured. As the drug product is intended for intravenous administration Osmolarity and pH of the solution play a vital role. So the drug product is designed to have comparable Osmolarity as that of RLD (Gemzar), in the pH range of 2.7 to 3.3. Based on the experimental results the Osmolarity of solution could be 510 mOsm/kg ±10% (Range 460 mOsm/kg to 560 mOsm/kg).Change in concentration of Mannitol did not result in significant change in pH of the solution. Whereas the increase in concentration of sodium acetate anhydrous resulted in higher pH of solution. The pH range of solution as specified in USP is 2.7 to 3.3. Increase in concentration of Mannitol or sodium acetate anhydrous or both results in the increase in Osmolarity of solution.
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