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Ketamine Hydrochloride 10-mg Troches

Loyd V. Allen, Jr, PhD
Professor Emeritus
College of Pharmacy, University of Oklahoma
Oklahoma City, Oklahoma



11/19/2009

US Pharm. 2009;34(11):58-59.

Method of Preparation: Calibrate the mold being used to determine the amount of polyethylene glycol (PEG) 1450 needed. Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Melt the PEG 1450 at 50°-55°C. Blend the powders (ketamine hydrochloride [HCl], silica gel, stevia, acacia, citric acid) and slowly sprinkle into melted base while mixing; mix until uniform. Remove from heat, add flavor (which can be based on the patient's preference), and mix well. Pour into molds and let mixture cool. Trim (if necessary), package, and label. 

Use: Ketamine HCl troches have been used to treat moderate-to-severe pain. 

Packaging: Package in well-sealed, light-resistant containers. 

Labeling: Keep out of the reach of children. Use only as directed. 

Stability: A beyond-use date of up to 6 months may be used for this preparation.1 

Quality Control: Quality-control assessment can include weight, specific gravity, active drug assay, color, texture-surface, appearance, feel, melting test, dissolution test, physical observation, and physical stability.2 

Discussion: Ketamine HCl (C13H16ClNO.HCl, MW 274.2), an analgesic and anesthetic, occurs as a white, crystalline powder with a slight characteristic odor. ≈1.15 mg is equivalent to 1 mg ketamine base. It is soluble 1 g in 4 mL water, 14 mL alcohol, and 60 mL absolute alcohol.1,3

Silica gel is obtained by insolubilizing the dissolved silica in sodium silicate solution. It occurs as a fine, white, hygroscopic, odorless, amorphous powder with a usual particle size of 2-10 mu. It is insoluble in alcohol, other organic solvents, and water, and soluble in hot solutions of alkali hydroxides. It is used as a desiccant, suspending agent, and viscosity-increasing agent.4

Stevia (honey leaf, yerba dulce) is a natural sweetening agent extracted from the Stevia rebaudiana Bertoni plant. Nontoxic and safe, it occurs as a white, crystalline, hygroscopic powder. It can be used in hot and cold preparations.5

Acacia (gum acacia, gum arabic) is the dried gummy exudate obtained from some species of the acacia tree. It is a complex aggregate of sugars and hemicelluloses, with MW from 240,000 to 580,000. It is used as an emulsifying agent (5%-10% concentration[conc]), pastille base (10%-30% conc), suspending agent (5%-10% conc), and tablet binder (1%-5% conc), as well as in cosmetics and food products. It should be preserved when in aqueous solution, as it is subject to bacterial or enzymatic degradation. Boiling its solution briefly will inactivate any enzymes and enhance its stability. Some substances that are incompatible with acacia are cresol, ethanol (95%), morphine, phenol, and thymol. Some salts reduce the viscosity of aqueous acacia solutions. Since acacia is negatively charged in solution, it will form a coacervate with positively charged molecules such as those in gelatin. Acacia may coagulate in the presence of trivalent salts.6

Citric acid (citric acid monohydrate, C6H8O7.H2O) occurs as colorless or translucent crystals or as a white, crystalline, efflorescent, odorless powder with a strong, tart, acidic taste. It is present at about the 5%-8% level in lemon juice. In 0.3%-2% concentration, it is used to improve flavor in liquid formulations and as a sequestering agent. It may be used to prepare effervescent granules and solid and semisolid (chewable) dosage forms. The hydrated form may contain up to 8.8% water, and the pH of a 1% w/v aqueous solution is ≈2.2. Its density is 1.542 g/mL. The hydrated form will effloresce and the anhydrous form will be hygroscopic, depending upon the humidity. If stored in air that is too dry, it may lose its water if the temperature reaches ≈40°C. Its melting point is ≈100°C, but it softens at ≈75°C. One g is soluble in <1 mL water and 1.5 mL ethanol. It is incompatible with potassium tartrate, alkali and alkaline earth carbonates, bicarbonates, acetates, and sulfides. If included in a syrup formulation, it may induce sucrose to crystallize.7

PEG 1450 (Carbowax, polyoxyethylene glycol) is an addition polymer of ethylene oxide and water. At room temperature, it occurs as a solid or as white or off-white waxy flakes or powder. Its density ranges from 1.15-1.21 g/mL; its melting point is 40°-48°C. It is soluble in water; miscible in all ratios with other PEGs; soluble in acetone, dichloromethane, ethanol, and methanol; and slightly soluble in aliphatic hydrocarbons and ether. It is insoluble in fats, fixed oils, and mineral oil.8 

REFERENCES

1. USP Pharmacists' Pharmacopeia. 2nd ed. Rockville MD: US Pharmacopeial Convention, Inc; 2008:217,775-779,1444.
2. Allen LV Jr. Standard operating procedure for performing physical quality assessment of suppositories, troches, lollipops and sticks. IJPC. 1999;3:56-57.
3. Sweetman SC, ed. Martindale: The Complete Drug Reference. 33rd ed. London, England: Pharmaceutical Press (PP); 2002:1262-1263.
4. Owen SC. Colloidal silicon dioxide. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association (APA); 2006:188-191.
5. Reynolds JEF, ed. Martindale: The Extra Pharmacopoeia. 30th ed. London, England: PP; 1993:1049.
6. Kibbe AH. Acacia. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: APA; 2006:1-3.
7. Amidon GE. Citric acid. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: APA; 2006:185-187.
8. Price JC. Polyethylene glycol. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: APA; 2006:545-550.
 

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