Abstract
To optimize the formulation of acetaminophen liquid suppository, the effect of additives on the physicochemical properties of liquid suppository base was investigated. The physi cochemical properties of P 407/P 188 (15/15%) (abbreviated in 15/15) and P 407/P l88 (15/20%) (abbreviated in 15/20) were measured after the addition of following additives; 2.5% acetaminophen as an active ingredient, vehicle components (5% ethanol, 5% propylene glycol, 5% glycerin), preservatives (0.1% sodium benzoate, 0,1% methylparahydroxybenzoate, 0.1% propylparahydroxybenzoate) and 1% of sodium chloride as an ionic strength controlling agent. Poloxamer gel was prepared with three different buffer solutions (pH 1.2, 4.0 and 6.8) and the physicochemical properties, gelation temperature, gel strength and bioadhesive force, were determined. In the results, the effect of additives on the physicochemical properties was dependent on their bonding capacities including hydrogen bonding and cross-linking bonding. Because the hydrogen-bonding capacities of acetaminophen, ethanol and propylene glycol were smaller than that of poloxamer, the binding force of poloxamer gel became weak by their putting in between poloxamer gel. Therefore, the gelation temperature (15/15, $35.7^{\circ}C$ vs 37.0, 39.4 $38.2^{\circ}C$; 15/20, $29.2^{\circ}C$ vs 31.2, 32.0, $30.3^{\circ}C$) increased, and gel strength (15/15, 4.03 see vs 2.72, 2.08, 3.12sec; 15/20, 300g vs 50, 50, 200g) and bioadhesive force (15/15, $6.8{\times}10^2\;dyne/cm^2$ vs 3.2, 6.0, $6.0{\times}10^2\;dyne/cm^2$; 15/20, $97.3{\times}10^2\;dyne/cm^2$ vs 11.1, 89.5, $92.0{\times}10^2\;dyne/cm^2$) decreased. Furthermore, the binding force of poloxamer gel became strong due to the hydrogen-bonding capacities of glycerin and the cross-liking bonding of sodium salt. Then, the gelation temperature (15/15, 35.0, $32.1^{\circ}C$; 15/20, 26.0, $21.0^{\circ}C$) decreased, and gel strength (15/15, 6.51 see, 300g; 15/20, 500, 650g) and bioadhesive force (15/15, 7.2, $81.6{\times}10^2\;dyne/cm^2$; 15/20, 112.3, $309.2{\times}10^2\;dyne/cm^2$) increased. The effect of pH on the physicochemical properties of poloxamer gel was dependent on the ingredients with which the buffer solutions were prepared. Poloxamer gels prepared with pH 1.2 and 4.0 buffer solutions had the increasing gelation temperature (15/15, 37.5, $38.1^{\circ}C$; 15/20, 33.1, $34.0^{\circ}C$) and the decreasing gel strength (15/15, 2.98, 3.81sec; 15/20, 200, 200g) and bioadhesive force (15/15, $7.0{\times}10^2dyne/cm^2$; 15/20, $74.0{\sim}88.1{\times}10^2dyne/cm^2$) owing to HCl. Poloxamer gel prepared with pH 6.8 buffer solutions had the decreasing gelation temperature (15/15, $27.2^{\circ}C$; 15/20, $22.3^{\circ}C$) and the increasing gel strength (15/15, 400g; 15/20, 550g) and bioadhesive force (15/15, $207.0{\times}10^2dyne/cm^2$; 15/20, $215.0{\times}10^2dyne/cm^2$) due to the cross-linking bonding of $NaH_2PO_4\;and\;K_2HPO_4$.
