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Tacrolimus 0.1% Topical Microemulsion

Loyd V. Allen, Jr., PhD
Professor Emeritus
College of Pharmacy, University of Oklahoma
Oklahoma City, Oklahoma



9/18/2013

US Pharm. 2013;38(9):47-48.

Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Mix together the propylene glycol (PG), polysorbate 80, Brij 30, isopropyl myristate, and tartaric acid solutions. Add the tacrolimus and purified water; mix well. Package and label.

Use: This preparation has been used in the treatment of plaque-type psoriasis therapy.

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 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: Tacrolimus, which is primarily used in transplantation procedures and for epicutaneous application in atopic dermatitis, is also effective in other chronic inflammatory dermatoses (e.g., psoriasis, lichen planus, sarcoidosis, and pyoderma gangrenosum). The formulation presented here penetrates the psoriatic skin.3

Tacrolimus (C44H69NO12.H2O, MW 822.03) is a potent macrolide immunosuppressant that is derived from Streptomyces tsukubaensis and has actions similar to those of cyclosporine. It occurs as colorless prisms that melt at about 128°C. Tacrolimus is soluble in methanol, ethanol, acetone, ethyl acetate, and ether, and it is practically insoluble in water.4

PG (C3H8O2) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste, somewhat resembling glycerin. It has a specific gravity of 1.038 g/mL and is miscible with acetone, 95% ethanol, glycerin, and water. PG is not miscible with fixed oils or light mineral oil. It will, however, dissolve some essential oils. PG is used as a humectant and preservative, and as a solvent or cosolvent. It is stable and may be mixed with numerous other solvents. Because PG is hygroscopic, it should be stored in an airtight container and protected from light.5

Polysorbate 80 (Tween 80, polyoxyethylene 20 sorbitan mono-oleate, C64H124O26, MW 1310) occurs as a yellow, oily liquid with a characteristic odor and a warm, somewhat bitter taste. It has a specific gravity of 1.06 to 1.09 and an HLB (hydrophilic-lipophilic balance) value of 15.0. It is stable in the presence of electrolytes, weak acids, and weak bases.6,7

Brij 30 (polyoxyethylene[4] lauryl ether, tetraethylene glycol dodecyl ether, Brij 35, C20H42O5, MW 362.54) occurs as a colorless to light-yellow liquid. It has a pleasant odor and a melting point of 14°C. It is miscible with water and has a specific gravity of 0.950. Brij 30 is used as a dispersing agent, emulsifying agent, gelling agent, nonionic surfactant, penetration enhancer, solubilizing agent, and viscosity-increasing agent.8

Isopropyl myristate (C17H34O2, MW 270.51) is composed of esters of propan-2-ol and saturated high-molecular-weight fatty acids. It is used as an emollient, solvent, skin penetrant, and oleaginous vehicle. It is absorbed readily by the skin and is used as a component of semisolid bases. Isopropyl myristate is a clear, colorless, practically odorless, mobile liquid with a bland taste. It has a specific gravity of 0.846 to 0.854, a boiling point of 140.2°C, and a freezing point of about 3°C. It is miscible with acetone, ethanol, ethyl acetate, fats, fatty alcohols, fixed oils, liquid hydrocarbons, and waxes; it is practically insoluble in glycerin, PG, and water.9

Tartaric acid (C4H6O6, MW 150.09) occurs as colorless or translucent crystals or as a white, fine to granular, crystalline powder that is odorless, has an acid taste, and is stable in air. It is highly soluble in water (1 g in 0.8 mL and 0.5 mL boiling water) and freely soluble in alcohol (1 g in 3 mL alcohol).1

REFERENCES

1. U.S. Pharmacopeia 35/National Formulary 30. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2012:334-386,1148.
2. Allen LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC. 1998;2:308-309.
3. Wohlrab J, Goebel A, Sherer D, et al. A topical tacrolimus microemulsion for plaque-type psoriasis therapy. Drug Dev Deliv. 2012;12:43-46.
4. Barrows LR. Antineoplastic and immunoactive drugs. In: Gennaro AR, ed. Remington: The Science and Practice of Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000:1502.
5. Weller PJ. Propylene glycol. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmaceutical Association; 2009:592-594.
6. Zhang D. Polyoxyethylene sorbitan fatty acid esters. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmaceutical Association; 2009:549-553.
7. Zhang D. Polysorbate 80. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmaceutical Association; 2009:549-553.
8. Gupta RT, Singh KK. Polyoxyethylene alkyl ethers. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Philadelphia, PA: Pharmaceutical Press; 2012:604-611.
9. Taylor AK. Isopropyl myristate. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmaceutical Association; 2009:348-349
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