Formulation effects on the mechanical and release properties of metronidazole suppositories

A study of the effects of Tween 20 and Tween 80 non-ionic surfactants, and witepsol H15 and polyethylene glycol (PEG) 2850 bases, on the mechanical and release properties of metronidazole suppositories was made. Mechanical strength was assessed by breaking strength values F. The values of F increased with increase in concentration of surfactant. The values of F for formulations containing Tween 20 were higher than those obtained for formulations containing Tween 80. Witepsol bases gave higher values of F than corresponding PEG bases. Release characteristics were assessed by the time for 80% drug release (t80), values of dissolution rate constants, k1 and k2 and the time of intersection, t1. The values of t80 decreased while those of k1 and k2 increased with increase in surfactant concentration. The values of t80 were lower, while those of k1 and k2 were higher, for formulations containing Tween 20 than for those formulations containing Tween 80. Witepsol bases gave lower t80 values and higher k1 and k2 values than their corresponding PEG bases. The concentration of surfactant, C, had the largest individual effect on the mechanical and release parameters while the nature of surfactant, S, had the lowest. The ranking for the individual effects of the variables on F and k1 was C > N >> S, on t80 and k2 was C >> N approximately = S, was on t1 was C = N = S. The interactions between S and C were largest for F, t80 and k2, and lowest for k1 and t1. The ranking of the interaction effects of the variables on F and k2 was S-C > N-C > N-S, on t80 was S-C > N-S approximately = N-C, on k1 was N-C > N-S > S-C, and on t1 was N-S = N-C > S-C. The results suggest that the individual and interaction effects of formulation variables would provide useful guides in optimizing metronidazole suppository formulations.