Trimethoprim and sulfamethoxazole suspension

Add and disperse Hydrogel 843T in approximately 8 mL purified water. 

Heat 30 mL purified water to 100°C and add to dispersion from step 1 with mixing. 

Load trimethoprim and 7 g sulfamethoxazole into a suitable mixer blend. 

Spread mass as small pancakes onto oven trays and dry at 50°C for approximately 14 hours. 

Charge approximately 350 mL water into a suitable stainless steel mixing tank. Add and dissolve saccharin with mixing. 

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Important specifications for the manufacture of all solutions include assay and microbial limits. Additional important specifications for suspensions include particle size of the suspended drug, viscosity, pH, and in some cases, dissolution. Viscosity can be important, from a processing aspect, to minimize segregation. In addition, viscosity has also been shown to be associated with bioequivalency. pH may also have some meaning regarding effectiveness of preservative systems and may even have an effect on the amount of drug in solution. With regard to dissolution, there are at least three products that have dissolution specifications. These products include pheny-toin suspension, carbamazepine suspension, and sulfamethoxazole and trimethoprim suspension. Particle size is also important, and at this point it would seem that any... 

It is important to consider the influence of interaction between functional groups of drugs that leads to their habit modification when formulated in suspension dosage form. Proton transfer from the N atom of sulfamethoxazole to the pyrimidine basic N1 atom of trimethoprim has been reported to occur in their equimolar complexes. Bettinetti et al. have reported nucleation of the complex of trimethoprim and sulfa-methoxypyridazine (1 1) to be accelerated by water or wet granulation. Our studies on cotrimoxazole (unpublished results) revealed immediate formation of fine needle-shaped crystals irrespective of the initial shape of sulfamethoxazole and trimethoprim crystals as a result of the interaction between the two drugs in suspension form. Small needles (Fig. 6A) were... 

Examples of a few oral suspensions in which a specific and well-defined particle-size specification for the drug substance is important include phenytoin suspension, car-bamazepine suspension, trimethoprim and sulfamethoxazole suspension, and hydrocortisone suspension. It is therefore a good idea to indicate particle size in the raw material specification, even though it is meant for dissolving in the processing, to better validate the manufacturing process while avoiding scale-up problems. 

Oral suspension 40 mg trimethoprim and Various, Bactrim Pediatric 200 mg sulfamethoxazole/5 mL (Rx) (Roche), Septra (GlaxoSmithKline)... 

Co-trimoxazole suspension (trimethoprim 160 mg with sulfamethoxazole 800 mg) was given to 8 healthy subjects, with and without 20 mL of kaolin-pectin suspension. The kaolin-pectin reduced the AUC and the maximum serum levels of the trimethoprim by about 12% and 20%, respectively. Changes in the sulfamethoxazole pharmacokinetics were not significant. The probable reason for this reduction in AUC is that trimethoprim is adsorbed onto the kaolin-pectin, which reduces the amount available for absorption. However, the reductions are small and unlikely to be clinically relevant. 

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