Suspensions metronidazole

Jim gets an ear infection and is started on metronidazole suspension. The current reflux regimen continues. 

What is the problem of using metronidazole suspension when the gastric content is acid suppressed ... 

The suspension (unlike the tablets) is made up of metronidazole benzoate. The benzoate must be cleaved by acid in order for the active metronidazole to be absorbed. Thus in neutral acid conditions the metronidazole suspension is likely to be less effective. 

O All symptomatic adults and children over the age of 8 years should be treated with metronidazole 250 mg three times daily for 7 days, or tinidazole 2 gas a single dose, or nitazoxanide 500 mg twice daily for 3 days.3 The pediatric dose of metronidazole is 15 mg/kg per day three times daily far 7 days. Alternative drugs include furazolidone 100 mg four times daily or paromomycin 25 to 30 mg/kg per day in divided doses daily for 7 days. Paromomycin may be used in pregnancy instead of metronidazole. Pediatric patients can also be treated with suspensions of either furazolidone 8 mg/kg per day in four divided doses far 7 days, or nitazoxanide (Alina) 100 to 200 mg every 12 hours for 3 days. 

Das and Haider described a simultaneous spectrophotometrie method for the analysis of binary dosage form mixtures of diloxanide furoate with metronidazole or with tinidazole [19], Powdered tablets or suspension, equivalent to 50 mg of the drug substances, were dissolved in 50 mL of dimethylformamide with shaking. After 15 minutes, the solution was diluted to 100 mL with water and filtered. A 1 mL portion of the filtrate was diluted to 50 mL with water, and the absorbance of the resulting solution measured at 320 and 262 nm for metronidazole and diloxanide furoate simultaneously. Alternatively, readings were taken at 318 and 262 nm for the simultaneous determination of tinidazole and diloxanide furoate. Recoveries were reported to be quantitative. 

Sadana and Gaonkar have simultaneously determined diloxanide furoate and tinidazole in pharmaceutical dosage form by gas liquid chromatography [37]. Powdered tablets or suspension formulations were dissolved in chloroform, the solution filtered, and then diluted to 25 mL with chloroform. The solution also contained metronidazole as an internal standard. A 600 nL aliquot was analyzed on a stainless steel column (1 m X 3.2 mm) containing 3% of OV-17 on Chlorosorb W-UP (100-120 mesh). The GC system was operated at 200°C, using nitrogen as the carrier gas (45 mL/min). Flame ionization detection was used to observe the analytes. 

Hoelgaard, A. and Moller, N. (1983). Hydrate formation of metronidazole benzoate in aqueous suspensions, Int. J. Pharm., 15 213-221. 

Oral 0.5, 1 g tablets 0.5 g/5 mL suspension Metronidazole(generic, Flagyl)... 

P. P. Pashankov and L. L. Kostova, Reversed-phase high-performance liquid chromatography of metronidazole benzoate in suspension dosage form, J. Chromatogr., 394 382 (1987). 

What is the other potential risk of using metronidazole alongside ranitidine suspension ... 

Ranitidine suspension is formulated with alcohol as an excipient (along with many other suspensions). Metronidazole may react with the alcohol in the blood to cause a disulhram-like reaction leading to flushing and tachycardia. 

Table 2.2 Oral bioavailability in horses of rifampin (5mg/kg aqueous suspension), metronidazole (20mg/kg aqueous suspension), pyrimethamine (1 mg/kg suspended in corn syrup), trimethoprim (5mg/kg) and sulphadiazine (25mg/kg oral paste combination preparation).

Grant et al. 1984), from which the enthalpy of solution can be calculated from the slope. If the lines intersect, it is known as the transition temperature, and one consequence of this is that there may be a transition from one polymorph to another, depending on the storage conditions. For example, the formation of the monohydrate of metronidazole benzoate from a suspension of the anhydrate was predicted from such data (Holgaard and Moller 1983). 

Hydrates can sometimes be obtained by simply suspending the anhydrous material in water, whereupon a form of Ostwald ripening occurs. For instance, aqueous suspensions of anhydrous metronidazole benzoate are metastable, and storage at temperatures lower then 38°C leads to monohydrate formation accompanied by crystal growth [65]. Sorbitol provides another example of this behavior, where slow cooling of a saturated aqueous solution yields long thin needles of sorbitol hydrate [66]. When suspended in water, anhydrous carbamazepine is transformed to carbamazepine dihydrate [67]. In other instances, hydrates can be obtained from mixed solvent systems. 

A monohydrate phase of metronidazole benzoate exhibited solubility properties different from those of the commercially available anhydrous form [37], The monohydrate was found to be the thermodynamically stable form in water below 38°C. The enthalpy and entropy changes of transition for the conversion of the anhydrate to the monohydrate were determined to be -1200 cal/mol and -3.7 cal/K mol, respectively. This transition was accompanied by a drastic increase in particle size and caused physical instability of oral suspension formula-... 

Insulin Zinc Suspension Metronidazole Phentermine Resin Erythromycin Stearate Phenobarbital Povidone-Iodine Quinidine Gluconate Hydroflumethiazide Imipramine Pamoate Methyl Phenidate Nitroglycerin... 

The bioavailability of a single 500-mg dose of metronidazole in 5 healthy subjeets was not significantly changed by 30 mL of a kaolin-pectin antid-iarrhoeal mixture. However, a 14.5% reduction in metronidazole bioavailability occurred with 30 mL of an aluminiiim hydroxide/simeticone suspension, and a 21.3% reduction occurred with a single 4-g dose of colestyramine. The clinical importance of these reductions is probably small, and no special precautions seem necessary. 

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