US Pharm. 2009;34(7):42-43.
Method of Preparation: Calculate the required quantity of each ingredient for the total amount to be prepared. Accurately weigh or measure each ingredient. Mix the myristyl nicotinate with the propylene glycol (PG) to form a smooth paste. Geometrically, incorporate the hydrophilic ointment into the mixture and mix until uniform. Package and label.
Note: Many different oil-in-water emulsion bases can be used for this preparation.
Use: Myristyl nicotinate topical cream has been used to limit the progression of actinic skin damage. It also possibly has been used to treat other conditions that involve impairment of the skin barrier.1
Packaging: Package in tight, light-resistant containers.2
Labeling: Keep out of the reach of children. Use only as directed. For external use only.
Stability: A beyond-use date of up to 30 days can be used for this preparation.2 Stability studies have found formulations to be stable at room temperature for 3 years, but the exact formulation presented here has not been tested.
Quality Control: Quality-control assessment can include theoretical weight compared with actual weight, pH, specific gravity (SG), active drug assay, color, texture, appearance, feel, rheologic properties, and physical observations.3
Discussion: Given the more than 1 million new cases of skin cancer and about 10 million cases of actinic keratosis in the United States annually, prevention and minimization, respectively, are important. Myristyl nicotinate has been used topically to limit the progression of skin damage and help keep skin cancers from forming.4
Nicotinic-acid esters have been used topically to treat various skin disorders. They are preferred over nicotinic acid because they serve as prodrugs and have desirable formulation properties for transdermal delivery. Also, esterases in the skin result in conversion to niacin and provide long release of the active ingredient.
Myristyl nicotinate (C20H33NO2, MW 319.48), a derivative of nicotinic acid, has been used to improve skin barrier function, mitigate signs of sun damage, and reduce the incidence of atopic dermatitis. Myristyl nicotinate has been found to be compatible with hydrocortisone, triamcinolone acetonide, metronidazole, and ketoconazole when formulated together, and it is photocompatible with retinoic acid.1
PG (C3H8O2) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste, somewhat resembling glycerin. It has an SG of 1.038 g/mL and is miscible with acetone, chloroform, 95% ethanol, glycerin, and water; it is not miscible with fixed oils or light mineral oil. It will, however, dissolve some essential oils. A 2% v/v aqueous solution of PG will be iso-osmotic with serum. PG is used as a humectant in topicals (≈15% concentration [conc]); as a preservative in solutions and semisolids (15%-30% conc); and as a solvent or cosolvent in aerosols (10%-30% conc), oral solutions (10%-25% conc), parenterals (10%-60% conc), and topicals (5%-80% conc). PG is actually a better solvent than glycerin. It is similar to ethanol as an antiseptic; it also is used in cosmetics and in the food industry as a vehicle for flavors and for emulsifiers. PG is stable and may be mixed with numerous other solvents. Aqueous solutions of PG can be sterilized by autoclaving. Since PG is hygroscopic, it should be stored in an airtight container and protected from light. Incompatibilities include potassium permanganate.5
Hydrophilic ointment is a water-washable, oil-in-water emulsion base containing methylparaben, propylparaben, sodium lauryl sulfate, PG, stearyl alcohol, white petrolatum, and purified water. It is miscible with water and aqueous solutions, and some amount of oil solutions can be incorporated into the inner phase of the emulsion.6,7 As mentioned previously, there are many different topical vehicles that can be used in place of hydrophilic ointment. Most studies of this preparation have used oil-in-water cream bases; lotions also have been used. If a lotion is desired, preserved purified water can be slowly added while mixing to the desired consistency. An adjustment in drug concentration may be required. Some products are available commercially, but the compounded preparation formula presented here can be individualized for specific patients.
REFERENCES
1. Tashtoush BM, Kim H, Jacobson EL, Jacobson MK. Formulation compatibility of myristyl nicotinate with drugs used to treat dermatological conditions involving an impaired skin barrier. Drug Dev Ind Pharm. 2007;33:1176-1182.
2. US Pharmacopeial Convention, Inc. USP Pharmacists' Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention, Inc; 2008:775-779.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC. 1998;2:308-309.
4. ClinicalTrials.gov. Topical myristyl nicotinate cream on the skin of healthy volunteers.
http://clinicaltrials.gov/ct2/
5. Owen SC, Weller PJ. Propylene glycol. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2006:624-626.
6. Reilly WJ Jr. Pharmaceutical necessities. In: Gennaro AR, ed. Remington: The Science and Practice of Pharmacy. 19th ed. Easton, PA: Mack Publishing Co; 1995:1402.
7. Block LH. Medicated applications. In: Gennaro AR, ed. Remington: The Science and Practice of Pharmacy. 19th ed. Easton, PA: Mack Publishing Co; 1995:1586.
