Physical and release properties of metronidazole suppositories

Purpose: A study was made of the effects of some bases and adjuvants on the physical and release properties of metronidazole suppositories with a view to providing more information for the optimization of the rectal formulation of metronidazole. Method: Suppositories (1g) containing 200mg of metronidazole each were prepared in witepsol (H15 and E75) and polyethylene glycol (PEG 2850 and 4650) bases; using different concentrations of Tween 80; sodium salicylate and methylcellulose as adjuvants. The setting time; solidification point and melting range of the suppositories were determined; along with their crushing strength; disintegration time and the time for 80of metronidazole to be released from the suppositories (t80). Results: The ranking of setting time for the suppositories was witepsol H15 PEG 2850 witepsol E75 PEG 4650; while the ranking of solidification point; melting range; crushing strength; disintegration time and the time for 80of metronidazole to be released from the suppositories (t80) was the reverse of that for setting time. Optimal concentrations of Tween 80 and sodium salicylate were observed for the suppository formulations. Using Kitazawa plots; all formulations showed two dissolution rate constants; k1 and k2 intersecting at time t1; with formulations containing 5 to 20w/w of methylcellulose exhibiting a third dissolution rate constant; k3 intersecting with k2 at time t2. Conclusion: The physical and release properties of metronidazole sup-positories are influenced considerably by the bases and adjuvants employed. Tween 80 and sodium salicylate can probably be used to formulate only immediate-release supposi- tories while methylcellulose can be useful for sustained-release metronidazole suppositories. Some insight into these inferences can be obtained from parameters derived from Kitazawa plots

Degradation kinetics of Metronidazole and its Mutual Prodrug with Ciprofloxacin : a Calorimetric Analysis

Calorimetric technique has aroused considerable interest as a versatile tool in pharmaceutical industry and academia to provide useful information about thermodynamic and kinetic aspects of drug molecules. The present paper utilizes this technique to monitor the hydrolytic degradation of metronidazole and its prodrug with ciprofloxacin; i.e. 2-(2-methyl-5-nitroimidazol-1-yl)ethyl-1-cyclopropyl-6-fluoro-1;4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylate. The synthesis of the present mutual prodrug was envisaged to combine the antiprotozoal and anaerobic antibacterial effects of metronidazole with antibacterial effects of ciprofloxacin. Heat flux microcalorimeter was used to determine the rate of heat evolved during the degradation of the drug and prodrug as a function of concentration; pH and temperature. In terms of enthalpy of hydrolysis the response is exothermic both for drug and prodrug. However; the absolute value of the enthalpy of reaction (?rH0) is low for the prodrug. The degradation followed pseudo first order kinetics; showed marked stability at pH 3-7 followed by accelerated hydrolysis at higher pH; characteristic of general acid-base catalysis. The catalytic rate constant for hydrogen ion (kH) and hydroxyl ion (kOH) were found to be 0.413 and 526.1 M-1h-1; respectively; at 318.15 K. The hydrolysis of the prodrug was found to be approximately 50-60 times faster than that of the drug. This may be attributed to the fact that hydrolysis of ester group in prodrug is assisted by keto group on the ciprofloxacin. However; there is no effect of protonation of nitrogen in piperazine ring in ciprofloxacin on the hydrolysis due to the distance from the ester moiety

Effects of dissolution medium; pH and temperature on the in vitro release properties of metronidazole tablets

The effects of dissolution medium; pH and temperature on the in vitro release properties of metronidazole; a commonly used antiprotozoal; from its tablet dosage forms have been studied. Metronidazole tablets were formulated using the conventional wet granulation technique. The standard tablet characteristics such as uniformity of weight; hardness and friabliity wer determined. Different dissolution media namely - simulated intestinal fluid (S. I. F.); simulated gastric fluid (S. G. F.) and buffer solutions (pH 2 to 11) were employed for disolution and disntegration studies. Similarly; disssolution studies were carrtied out at varying temperatures to determine the effect of temperature onn release and disintegration. Results obtained showed that the tablets possessed officailly acceptable hardness; uniformity of weight; and absolute drug content; but a high friablity. The drugs were released faster in the less acidic S. I. F. than in th S. G. F. while the dissolution and disintegration rates increased as the pH increased.. Temperature also increased the dissolution and disintegration rates