IDENTIFICATION OF FACTORS AFFECTING PRESERVATIVE EFFICACY AND CHEMICAL-STABILITY OF LAMIVUDINE ORAL SOLUTION THROUGH STATISTICAL EXPERIMENTAL-DESIGN

To identify factors affecting the chemical stability and preservative efficacy of lamivudine oral liquid formulations, an optimization study using a central composite design was performed. In this design, five factors, each at three levels, were investigated: pH (4.5, 5.5, and 7. 5), sucrose (5%, 20%, and 50% w/v), propylene glycol (0%, 2%, and 5% w /v), glycerin (4%, 8%, and 12% w/v), and EDTA (0.100, 0.175, and 0,250 mg/mL). All formulations contained a constant concentration of lamivu dine, parabens, and artificial strawberry and banana flavors. All form ulations were evaluated for preservative effectiveness against USP and BP standards and for chemical stability at 30 degrees C and 40 degree s C for three months. All formulations were effective against bacteria and yeasts, but indicated reduced preservative effectiveness against the mold Aspergillus niger. Preservative effectiveness improved with i ncreasing pH (4.5 to 7.5) and to a lesser extent with increasing EDTA concentration (0.100 to 0.250 mg/mL). Increasing glycerin concentratio n (4% to 12% w/v) slightly decreased preservative effectiveness. Over the concentration ranges tested, no change in preservative effectivene ss was noted with concentration changes in sucrose or propylene glycol . The pH was the main factor influencing the chemical stability of the drug and preservatives in this study. Lamivudine chemical stability i ncreased with increasing pH from 4.5 to 7.5. Methyl and propylparaben showed extensive degradation at pH 7.5.