Amitriptyline 10%, Baclofen 2.5%, and Ketamine 5% in PLO Gel

 

US Pharm. 2015;40(3):48-49.

Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Mix the three powders with the ethoxydiglycol to form a smooth paste. Incorporate the mixture into the isopropyl palmitate:lecithin and mix well. Add the Pluronic F127 gel and mix using a shear-mixing method until uniform. Package and label.

Use: This preparation has been used in the treatment of pain.

Packaging: Package in tight, light-resistant containers.

Labeling: Keep out of reach of children. Discard after ____ [time period].

Stability: A beyond-use date of up to 30 days may be used for this preparation.¹

Quality Control: Quality-control assessment can include theoretical weight compared with actual weight, pH, specific gravity, active drug assay, color, texture-surface, texture-spatula spread, appearance, feel, rheologic properties, and physical observations.²

Discussion: This “pain gel” has been used in the treatment of pain with or without the oral administration of analgesic drugs. There are hundreds of different combinations of pain drugs and concentrations in current use today that are being routinely compounded. Close monitoring of the patient is important.

Amitriptyline HCl (Elavil, C₂₀H₂₃N.HCl, MW 313.86) occurs as a white or practically white, odorless or practically odorless, crystalline powder or as small crystals. It is freely soluble in water, alcohol, and methanol. The pH of a 1-in-100 solution of amitriptyline HCl is between 5.0 and 6.0.¹

Baclofen (Lioresal, C₁₀H₁₂ClNO₂, MW 213.66) occurs as a white to off-white, crystalline powder that is odorless or nearly odorless. It is slightly soluble in water. Baclofen is a gamma–butyric acid derivative used as a skeletal muscle relaxant. Baclofen reduces the frequency and amplitude of muscle spasms (tonic reflexes) arising in response to muscle stretching in patients with various spinal cord lesions.¹

Ketamine HCl (C₁₃H₁₆ClNO.HCl, MW 274.2) is used as an anesthetic and analgesic. It occurs as a white, crystalline powder with a slight characteristic odor. Ketamine is soluble 1 g in 4 mL of water, 14 mL of alcohol, and 60 mL of absolute alcohol.^1,3

Ethoxydiglycol (C₆H₁₄O₃, CH₂OHCH₂OCH₂CH₂OC₂H₅, MW 134.20) occurs as a colorless liquid with a mild, pleasant odor. It is hygroscopic and is miscible with water and common organic solvents. Ethoxydiglycol has a density of 1.0272; it has a boiling point of 195°C to 202°C and is combustible. Ethoxydiglycol is nonirritating and nonpenetrating when applied to human skin, and it is used as a solvent, solubilizer, and cosurfactant.⁴

Isopropyl palmitate (C₁₉H₃₈O₂, MW 298.51) is a colorless, mobile liquid with a very slight odor that is used as an emollient, oleaginous vehicle, and solvent; it has good spreading characteristics. Isopropyl palmitate is soluble in acetone, castor oil, cottonseed oil, alcohol, and mineral oil. It is insoluble in water, glycerin, and propylene glycol.⁵

Lecithin (egg lecithin, soybean lecithin, vegetable lecithin) describes a complex mixture of acetone-insoluble phosphatides in combination with triglycerides, fatty acids, and carbohydrates. Lecithin is used as an emollient, emulsifying agent, and solubilizing agent in topicals. It is practically insoluble in water, polar solvents, and cold vegetable and animal oils.⁶

Pluronic F127, a block copolymer of ethylene oxide and propylene oxide, is used as an emulsifying agent, solubilizing agent, and wetting agent. Pluronic F127 occurs as white-colored, waxy, free-flowing granules that are practically odorless and tasteless. The pH of a 2.5% w/v aqueous solution is in the range of 6.0 to 7.4. Pluronic F127 is generally available in powdered form, and it is odorless or may have a very mild odor. It melts at about 56°C and is freely soluble in water, alcohol, and isopropyl alcohol.⁷

REFERENCES

1. U.S. Pharmacopeia 38/National Formulary 33. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2014:559-611,1919,1922,1945.
2. Allen LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC. 1998;2:308-309.
3. Sweetman SC, ed. Martindale: The Complete Drug Reference. 33rd ed. London, England: Pharmaceutical Press; 2002:1262-1263.
4. Ash M, Ash I. Handbook of Pharmaceutical Additives. Brookfield, VT: Gower Publishing Ltd; 1995:484.
5. Taylor AK. Isopropyl palmitate. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:400-402.
6. Shah HC, Sheng JJ. Lecithin. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:437-439.
7. Cable CG. Poloxamer. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:573-577.

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