Epinephrine

METHOD OF PREPARATION

1. Calculate the required quantity of each ingredient for the total amount to be prepared.

2. Accurately weigh and/or measure each ingredient.

3. Add the methylparaben, propylparaben and hydroxyethylcellulose to about 90 mL of purified water and mix well.

4. Heat to about 70-80°C with stirring until the ingredients have dissolved.

5. Cool to room temperature and add the lidocaine hydrochloride, epinephrine hydrochloride and tetracainc hydrochloride and stir until dissolved.

6. Add sufficient purified water to volume and mix well.

7. Package and label.

PACKAGING

Package in tight, light-resistant containers.1

LABELING

Keep out of reach of children. Protect from light. Keep in a cool place. For professional use.

STABILITY

A beyond-use date of up to 14 days, when stored in a refrigerator, can be used for this preparation.1

USE

Lidocaine-epinephrine-tetracaine (LET) spray is used to produce local anesthesia in selected patients, generally for minor surgical procedures and emergency room use.

QUALITY CONTROL

Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, clarity, rheological properties/pourability, physical observation and physical stability (discoloration, foreign materials, gas formation, mold growth).2

DISCUSSION

Lidocaine hydrochloride (C^sub 14^H^sub 22^N^sub 2^O.HCl.H2O, MW 288.81) occurs as a white, odorless, crystalline powder with a slightly bitter taste. It is an amide-type local anesthetic with a rapid onset and intermediate duration of action. It is very soluble in water (1:0.7) and in alcohol (1:1.5).2 A 0.5% aqueous solution has a pH in the range of 4.0 to 5.5. It should be protected from light. Approximately 1.16 g of lidocaine hydrochloride is equivalent to 1 g of lidocaine.3

Epinephrine hydrochloride (C^sub 9^H^sub 13^NO^sub 3^.HCl, MW 219.7, adrenaline hydrochloride) is a sympathomimetic agent. Epinephrine hydrochloride injection USP has a pH in the range of 2.5 to 5 and should be protected from light. It should not be used if it contains a precipitate.3

Tetracaine hydrochloride (C^sub 15^H^sub 24^N^sub 2^O^sub 2^.HCl, MW 300.82, amethocaine hydrochloride) occurs as a fine, white, crystalline, odorless powder. It has a slightly bitter taste, which is followed by a sense of numbness. It is hygroscopic and very soluble in water (1:7.5) and soluble in alcohol. A 1% aqueous solution has a pH in the range of 4.5 to 5.5; the USP specifies a pH of 5.0-6.0 for a 1% aqueous solution; the USP injection has a pH in the range of 3.2 to 6.0.2,3

Hydroxyethylcellulose (HEC) occurs as a light tan or cream-to-white-colored, odorless and tasteless powder. HEC is a non-ionic, water-soluble polymer used especially as a thickening agent in ophthalmic formulations. It is soluble in hot or cold water but practically insoluble in acetone, ethanol and most organic solvents. Solutions can be easily made by dispersing HEC in mildly agitated water at room temperature. When the powder has been thoroughly wetted, increasing the temperature to 60-70°C speeds up the dispersion process.4

Methylparaben (C^sub 8^H^sub 8^O^sub 3^, MW 152.15, Methyl hydroxybenzoate, Methyl parahydroxybenzoate) is available as colorless crystals or as a white, crystalline powder that is odorless or almost odorless, and has a slight burning taste. One gram is soluble in 400 mL of water.5

Propylparaben (C^sub 10^H^sub 12^O^sub 3^, MW 18.20, Propyl hydroxybenzoate, Propyl parahydroxybenzoate) is available as a white, crystalline, odorless and tasteless powder. One gram is soluble in 2500 mL of water.6

Purified water is water that is obtained by distillation, ion exchange, reverse osmosis or some other suitable process.7

REFERENCES

1. US Pharmacopeial Convention, Inc. United States Pharmacopeia 27-National Formulary 22. Rockville, MD: US Pharmacopeial Convention, Inc.; 2004: 2345-2349,

2. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC 1999; 3: 146-147.

3. Reynolds JEF, ed. MARTINDALE: The Extra Pharmacopoeia. 30th ed. London: Pharmaceutical Press; 1993: 1-6, 1001-1002, 1010-1014, 1057.

4. Harwood RJ. Hydroxyethylcellulose. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 283-286.

5. Reiger MM. Methylparaben. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 390-394.

6. Rieger MM. Propylparaben. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 526-528.

7. Ellison A, Nash RA, Wilkin MJ. Water. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 672-676.

Copyright International Journal of Pharmaceutical Compounding Nov/Dec 2004
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