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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.

The individual and interaction effects of nature of binder (N), concentration of binder (C) and the physical form of the formulation (P) on the tensile strengths (T--a measure of the bond strength of tablets) and the brittle fracture index values (BFI--a measure of the lamination tendency of tablets) of metronidazole tablets have been studied using a 2(3) factorial experimental design in each case. Changing binder concentration from a 'low' to a 'high' level increased T and reduced the BFI of the tablets. Methylcellulose 20 exhibited stronger binding effect and greater ability to reduce the lamination tendency of the tablets than polyvinylpyrrolidone of molecular weight 44,000. Granular formulations produced tablets with lower T values but also with lower BFI values than tablets produced from powdered formulations. The ranking of these individual effects on tensile strength was P greater than C greater than N while the ranking for the BFI was P greater than N greater than C. For the interaction effects, the ranking for tensile strength was P-N much greater than N-C greater than P-C while the ranking for the BFI was N-C much greater than P-C greater than P-N.

Incorporating polyvinylpyrrolidone, gelatin and methylcellulose binding agents in a metronidazole formulation alters the tensile strength, disintegration and dissolution times of the tablets by reducing their wettability as measured by the adhesion tension of water. Correlations have been established between the disintegration times, D and the dissolution times t50, t90 and t1 (derived from the equation of Noyes & Whitney). A correlation has also been established between the adhesion tension of water on the tablets and the disintegration and dissolution times. These correlations depend on the nature and concentration of binder used.

A study has been made of the effects of polyvinylpyrrolidone, gelatin and methylcellulose binding agents on the fundamental and tableting properties of a metronidazole-lactose-starch formulation. A material constant, alpha, was derived from the measured values of tensile strength of the materials. The values of alpha for the formulations are lower than that for metronidazole and depend on the nature and concentration of binder present. In terms of tableting properties, alpha supplements the information obtained from the ratios of elastic recovery to plastic compression (ER/PC) and from the brittle fracture index values (BFI) of the materials, although its influence appears to be limited at low values of ER/PC.