Amitriptyline HCl 2%, Carbamazepine 2%, Gabapentin 10%, and Ketoprofen 2% in Transdermal Pain Base

US Pharm. 2017;42(3):HS14-HS17.

Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Blend the powders until mixture is uniform. Add ethoxydiglycol or propylene glycol and mix to form a smooth, uniform paste. Geometrically, incorporate paste into the Transdermal Pain Base and mix until uniform. Package and label.

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

Packaging: Package in tight, light-resistant containers.

Labeling: Keep out of reach of children. For external use only. Discard after ____ [time period].

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

Quality Control: Numerous combinations of drugs are used in transdermal-delivery vehicles for topical treatment of pain and many other disorders. This is one example, and the percentages of active ingredients may be easily adjusted based on the patient’s response.

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

Discussion: Amitriptyline hydrochloride (Elavil, C₂₀H₂₃N.HCl, MW 313.86) is a dibenzocycloheptene-derivative tricyclic antidepressant that shares the pharmacologic actions, uses, and potential toxicity of the tricyclic antidepressants. It occurs as a white or practically white, odorless or practically odorless, crystalline powder or small crystals. Amitriptyline hydrochloride is freely soluble in water, alcohol, and methanol, and it melts between 195°C and 199°C. Amitriptyline hydrochloride should be preserved in well-closed containers.¹

Carbamazepine (Tegretol, C₁₅H₁₂N₂O, MW 236.27) occurs as a white to off-white powder that is practically insoluble in water and soluble in alcohol. Carbamazepine is an iminostilbene derivative used both as an anticonvulsant and for the relief of pain associated with trigeminal neuralgia; it is also used for psychiatric disorders such as schizophrenia and bipolar disorder.¹

Gabapentin (Neurontin, cyclohexaneacetic acid, C₉H₁₇NO₂, MW 171.24) occurs as a white to off-white, crystalline solid that is freely soluble in water and in alkaline and acidic solutions. Gabapentin is an anticonvulsant that is structurally related to gamma-aminobutyric acid. It is used in combination with other anticonvulsants in the management of seizure disorders, neuropathic pain, and vasomotor symptoms, as well as in the treatment or management of epilepsy, headache, hiccups, hot flushes, Lesch-Nyhan syndrome, motor neuron disease, multiple sclerosis, parkinsonism, postoperative pain, some psychiatric disorders, restless legs syndrome, soft-tissue rheumatism, stiff-man syndrome, and tremor.³

Ketoprofen (C₁₆H₁₄O₃, MW 254.28) occurs as a white or almost white, odorless or almost odorless, crystalline powder. It is practically insoluble in water, but is freely soluble in alcohol and ether. Ketoprofen has a melting range between 92.0°C and 97.0°C. It has analgesic, anti-inflammatory, and antipyretic properties and is an inhibitor of cyclooxygenase. Ketoprofen should be preserved in tight containers.¹

Ethoxydiglycol (diethylene glycol monoethyl ether, diethylene glycol ethyl ether, Carbitol, Transcutol, CH₂OHCH₂OCH₂CH₂OC₂H₅, C₆H₁₄O₃, MW 134.20) occurs as a colorless liquid with a mild, pleasant odor. It is hygroscopic and is miscible with water and with common organic solvents. Ethoxydiglycol has a density of 1.0272, and it is combustible. Ethoxydiglycol is nonirritating and nonpenetrating when applied to human skin, and it is used as a solvent, solubilizer, and cosurfactant.⁴

Propylene glycol (C₃H₈O₂) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste somewhat resembling that of glycerin. It has a specific gravity of 1.038 g/mL and it is miscible with acetone, 95% ethanol, glycerin, and water. Propylene glycol is not miscible with fixed oils or light mineral oil; it will, however, dissolve some essential oils. Propylene glycol is actually a better solvent than glycerin.⁵

Transdermal Pain Base (Medisca) is a highly versatile, off-white, oil-in-water, pluronic lecithin organogel (PLO) cream that exhibits an increased carrying capacity for both lipophilic and hydrophilic drugs and their salt forms. It is ideal for pharmaceutical compounding of increased amounts of actives (greater than or equal to 10%). Transdermal Pain Base is a vehicle for lipophilic and hydrophilic drugs and has a characteristic PLO odor.⁶

REFERENCES

1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; February 2017.
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. 36th ed. London, England: Pharmaceutical Press; 2009:482-484.
4. Ash M, Ash I. Handbook of Pharmaceutical Additives. Brookfield, VT: Gower Publishing Ltd; 1995:484.
5. Ladyzhynsky NS. Propylene glycol. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:672-674.
6. Transdermal Pain Base product details. www.medisca.com/Pages/ProductDetails.aspx?StockCode=2493&C=B&C2=108. Accessed February 16, 2017.

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