Oral administration suspending vehicles

Orally administered suspensions containing a wide class of active ingredients (e.g., antibiotics, antacids, radiopaque agents) are of major commercial importance. The solids content of an oral suspension may vary considerably. For example, antibiotic preparations may contain 125-500 mg solid drug per 5 mL or a teaspoonful dose, while a drop concentrate may provide the same amount of drug in only 1-2 mL. Antacid or radiopaque suspensions also contain relatively high amounts of suspended material for oral administration. The suspending vehicle can, for example, be a syrup, sorbitol solution, or gum-thickened water with added... 

The physical form of a material destined for oral administration often presents unique challenges. Liquids can be administered as supplied or diluted with an appropriate vehicle, and powders or particulates can often be dissolved or suspended in an appropriate vehicle. However, selection of an appropriate vehicle is often difficult. Water and oil (such as the vegetable oils) are used most commonly. Materials that are not readily soluble in either water or oil can frequently be suspended in a 1% aqueous mixture of methylcellulose. Occasionally, a more concentrated methylcellulose suspension (up to 5%) may be necessary. Materials for which appropriate solutions or suspensions cannot be prepared using one of these three vehicles often present major difficulties. 

Figure 7.26(a) Representative plasma concentrations of griseofulvin following oral administration of 50 mg/kg of griseofulvin suspended in lipid vehicles and water. Each curve, representing data from one animal, has a peak plasma concentration and fmax closest to the mean values for each group. For key, see Fig. 7.25. Inset correlation of the area under the plasma concentration-time curve (AUC) with the average 0 to 4 h rate of release of griseofulvin in vitro, (b) Release of griseofulvin into water from suspensions containing 5 mg drug in lipid and water. Each point represents the mean of three experiments. Key as above. From Bloedow and Hay ton [79] with permission.

Rats weighing 180-240 g are kept on standard diet. Groups of 8 non-fasted animals are treated orally with various doses of the test compounds suspended in 0.4% starch suspension. One control group receives the vehicle only. Blood is withdrawn from the tip of the tail immediately before, and 1,2,3,5, and 24 hours after administration of the candidate compound. Blood glucose is determined in 10 pi blood samples collected from the tip of the tail. If pharmacokinetic data for the candidate compound are already available, when performing this test, additional blood samples (100 pi) should be taken at max by retro orbital bleeding for detection of free fatty acids, triglycerides and insulin. 

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