Mannitol is available as a 10, 15, or 20% injection solution in single-dose flexible plastic containers and a 25% injection solution in 50-mL single-dose vials.4067; 4068 Each mL of the 10, 15, or 20% solution contains mannitol 100, 150, or 200 mg, respectively, with sodium hydroxide or hydrochloric acid for pH adjustment.4067 Each mL of the 25% solution contains mannitol 250 mg and may contain sodium bicarbonate and/or hydrochloric acid for pH adjustment.4068
Table 1. Characteristics of Mannitol Products4067; 4068
| Concentration (%) | Concentration (g/L) | Osmolarity (mOsm/L) | pH | Available Sizes |
|---|---|---|---|---|
| 10 | 100 | 549 | 5 (4.5 to 7) | 500 mL flexible plastic container |
| 15 | 150 | 823 | 5 (4.5 to 7) | 500 mL flexible plastic container |
| 20 | 200 | 1098 | 5 (4.5 to 7) | 250 mL flexible plastic container 500 mL flexible plastic container |
| 25 | 250 | 1372 | 5.9 (4.5 to 7) | 50 mL vial |
pH
From 4.5 to 7.4067; 4068 (See Table 1.)
Osmolarity
The osmolarities of mannitol injection solutions are listed in Table 1.
Trade Name(s)
Osmitrol
Mannitol is administered by intravenous infusion, preferably through a large central vein.4067; 4068 An administration set with a filter should be used because of the potential for mannitol crystals to form in the solution.4067; 4068
Mannitol solutions should be stored at controlled room temperature.4067; 4068 Protect from freezing.4068 Brief exposure up to 40°C does not adversely affect the product; however, excessive heat should be avoided.4067
Mannitol solution should not be transferred into PVC bags because a white flocculent precipitate may form from contact with PVC surfaces.4068
Crystallization
Mannitol solutions may crystallize when exposed to low temperatures.593; 4067; 4068 Higher concentrations of mannitol solutions have a greater tendency to crystallize.4067 Mannitol solutions should be inspected for crystals prior to use.4067; 4068 If crystallization occurs, mannitol in flexible plastic containers may be warmed up to 70°C with agitation.4067 Do not heat flexible plastic containers in water or by microwave radiation due to potential for product contamination or damage.4067 Mannitol 25% in vials may be warmed in water up to 80°C with vigorous shaking.4068 Mannitol 25% in vials also may be autoclaved at 121°C for 20 minutes at 15 psi.4068 Allow solutions to cool to room or body temperature and reinspect for crystals.4067; 4068 Discard solution if crystals cannot be dissolved.4068
The use of a microwave oven to resolubilize crystallized mannitol in glass ampuls has been suggested. Exposure to microwave radiation followed by shaking satisfactorily resolubilized the crystals in a shorter total time than the water bath and autoclave methods and resulted in no chemical decomposition.694
Unfortunately, the use of microwave radiation to solubilize mannitol crystals is a highly risky undertaking. Explosions of mannitol ampuls during microwave exposure have been reported.695; 697 Such explosions could injure someone as well as ruin the microwave oven. The explosion results from pressure building during the heating of the solution that occurs from the microwave exposure.696; 697
One inventive pharmacist redissolved mannitol crystals using a coffeemaker.1114
As an alternative to resolubilizing techniques, the use of warming chambers to maintain the solutions in a crystal-free condition has been recommended.698; 699; 700 Various chambers have been described, including a wooden cabinet,698 a metal kettle,699 and even a bun warmer.700 Storage temperatures of 35 and 50°C have been utilized.698; 699
A related but differing effect is seen when supersaturated solutions of mannitol are placed in polyvinyl chloride (PVC) bags. Within a few minutes, a heavy white flocculent precipitate forms. The needle-like crystals in mannitol solutions result from slow undisturbed growth. The white flocculent mannitol precipitate results from contact with the PVC surfaces, which act as nuclei for rapid crystallization of small crystals. Attempts to resolubilize the precipitate with the aid of heat are not fruitful because crystallization may recur in a short time.432
AutoclavingMannitol 25% in vials may be autoclaved at 121°C for 20 minutes at 15 psi.4068
Mannitol 25% was chemically and physically stable after 5 autoclavings at 250°F for 15 minutes. In addition, no extracts or visible particles from the rubber closures were found.83
For a list of references cited in the text of this monograph, search the monograph titled References.