Betamethasone Valerate 0.1% and Neomycin Sulfate 0.6% Gel-Cream

US Pharm. 2013;38(3):20-21.

Method of Preparation: Note—It may be necessary to adjust the neomycin sulfate quantity based upon the assay of the specific lot being used.

Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Mix the polyethylene glycol (PEG) 300 with the Miglyol 812. Dissolve the Pluronic F127 and neomycin sulfate in about 60 mL of purified water at refrigerated temperature. Mix both solutions. Add sufficient cold purified water to final volume and mix well. Store in a refrigerator until all air bubbles have disappeared. Package and label.

Use: This preparation has been used for the treatment of minor skin disorders.

Packaging: Package in tight, light-resistant containers.

Labeling: For external use only. 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 may 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: Betamethasone valerate (C₂₄H₃₁FO₆, MW 434.50) is a synthetic fluorinated corticosteroid that occurs as a white to practically white, odorless powder. It melts at about 190°C with decomposition and is freely soluble in acetone, soluble in alcohol (1 g in 16 mL), and practically insoluble in water (1 g in 10,000 mL).¹ Betamethasone valerate is used as a topical anti-inflammatory agent.

Neomycin sulfate is an aminoglycoside antibiotic obtained from cultures of Streptomyces fradiae. It occurs as a white to slightly yellow, hygroscopic powder that is freely soluble in water and very slightly soluble in alcohol. It should be stored in tight, light-resistant containers. Neomycin sulfate has a potency equivalent of not less than 600 mcg of neomycin per mg, calculated on the dried basis.^1,3

PEG 300 (Carbowax, polyoxyethylene glycol) is an addition polymer of ethylene oxide and water. It occurs as a clear, colorless or slightly yellow-colored, viscous liquid with a slight, characteristic odor and a bitter, slightly burning taste. The density of PEG 300 is 1.11, and the freezing point is –15°C to –8°C. It is soluble in water and miscible in all ratios with other PEGs; it also is soluble in acetone, alcohols, glycerin, and glycols.⁴

Miglyol 812, a medium-chain triglyceride (MCT), is the fixed oil extracted from the hard, dried fraction of the endosperm of Cocos nucifera L. or the dried endosperm of Elaeis guineensis Jacq. MCTs consist of a mixture of triglycerides of saturated fatty acids, mainly caprylic acid and capric acid. They occur as a colorless to slightly yellowish, oily liquid that is practically odorless and tasteless and solidifies at about 0°C. MCTs are used in oral, parenteral, and topical formulations as emulsifying, solvent, suspending, and therapeutic agents. Low-density polyethylene should not be used as the packaging material, as MCTs will readily penetrate the plastic (especially at high temperatures) and result in an oily film on the outside of the container. Also, polyvinylchloride should be tested for compatibility, since MCTs can dissolve some plasticizers, such as phthalates, out of the plastic container.⁵

Pluronic F127 is a poloxamer. Poloxamers are a series of closely related block copolymers of ethylene oxide and propylene oxide that are used as emulsifying agents, solubilizing agents, and wetting agents. Poloxamers generally are white-colored, waxy, free-flowing granules or cast solids 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. Poloxamers are stable and aqueous solutions are stable in the presence of acids, alkalis, and metal ions, but the aqueous solutions support mold growth. Poloxamer 407 (Pluronic F127) is generally available in powdered form. 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.⁶

Purified water is water that is obtained by distillation, ion exchange, reverse osmosis, or some other suitable process. It is miscible with most polar solvents and is chemically stable in all physical states (ice, liquid, and steam).⁷

REFERENCES

1. U.S. Pharmacopeia 35/National Formulary 30. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2012:344-350,1131.
2. Allen LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC. 1998;2:308-309.
3. McEvoy GK, ed. AHFS Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists; 2012:3497-3498.
4. Wallick D. Polyethylene glycol. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmaceutical Association; 2009:517-522.
5. Moss G. Medium-chain triglycerides. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmaceutical Association; 2009:429-431.
6. Collett JH. Poloxamer. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmaceutical Association; 2009:506-509.
7. Dubash D, Shah U. Water. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:880-884.

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