Monthly Compounding Update
    Estriol 2 mg and Estradiol 0.5 mg per 0.1 mL Sublingual Drops
  This formulation can be used in bioidentical hormone therapy.
Loyd V. Allen, Jr., PhD
Professor Emeritus, College of Pharmacy, University of Oklahoma, Oklahoma City
Estriol 2 mg and Estradiol 0.5 mg per 0.1 mL Sublingual Drops
Rx (for 10 mL):
Silica gel
Flavor oil
Almond oil   qs
200 mg
50 mg
100 mg
200 mg
10 mL
US Pharmacist

Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Triturate the estriol, estradiol, saccharin, and silica gel in a mortar. Add a small amount of almond oil and triturate to a smooth paste. Add sufficient flavor, followed by additional almond oil to volume, and mix well. Package and label.

Use: Estriol and estradiol sublingual drops are used in bioidentical hormone replacement therapy.

Packaging: Package in tight, light-resistant containers.

Labeling: Keep out of reach of children. Use only as directed. Discard after ____ [time period].

Stability: A beyond-use date of up to 6 months may be used for this preparation.1

Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth).2

Discussion: Estriol, a naturally occurring estrogen, is claimed to have a selective action on the cervix, vagina, and vulva and to have relatively little effect on the endometrium. It is often given in combination with estrone and estradiol in estrogen replacement therapy. Estriol is a crystalline powder that is practically insoluble in water, but soluble in alcohol and vegetable oils. In the body, estradiol is reversibly oxidized to estrone, and both estradiol and estrone can be converted to estriol.1,3,4

Estradiol is a naturally occurring steroidal estrogen that occurs as white or creamy white, small crystals or as a crystalline powder. It is odorless, hygroscopic, and practically insoluble in water, but it has a solubility of about 35.7 mg/mL in alcohol at 25°C. Estradiol should be stored in tight, light-resistant containers. Generally, estradiol is not used orally, owing to extensive first-pass hepatic metabolism, but this effect can be minimized by sublingual administration and absorption.1,4-6

Saccharin (C7H5NO3S, MW 183.18) is an intense sweetening agent widely used in commercial products, including foods, drinks, and pharmaceuticals. It is used in oral formulations as a sweetener, generally in concentrations ranging from 0.02% to 0.5%. Saccharin is about 500 times sweeter than sucrose and can be used to mask some unpleasant tastes of various medications. It occurs as odorless, white crystals or as a white, crystalline powder. Along with its intensely sweet taste, saccharin has a metallic aftertaste that is experienced by about 25% of the population. It is soluble to the extent of 1 g in 290 mL of water, in 50 mL of glycerin, and in 31 mL of 95% ethanol.7 For aqueous preparations, the sodium salt is used.7

Silica gel, a form of silicon dioxide, is obtained by insolubilizing the dissolved silica in sodium silicate solution. Silica gel occurs as a fine, white, hygroscopic, odorless, amorphous powder with a usual particle size ranging from 2 µm to 10 µm. It is insoluble in water, alcohol, and other organic solvents. Silica gel is used as a desiccant, suspending agent, and viscosity-increasing agent.1,8

Almond oil (sweet almond oil) is a clear, pale straw-colored or colorless, almost odorless, oily liquid with a bland, nutty taste. It contains primarily glycerides of oleic acid, with smaller amounts of linoleic, myristic, and palmitic acids. Almond oil is expressed, without heat, from the seeds of the bitter almond or the sweet almond. Its specific gravity is 0.910 to 0.915. Almond oil is slightly soluble in alcohol, but miscible with mineral oil. It should be protected from light and stored in a cool place and in well-filled, airtight containers.1

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1. United States Pharmacopeia 38/National Formulary 33. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2014:559-567,1918,1936,1937,1965.
2. Allen LV Jr. Standard operating procedure for quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
3. Reynolds JE, ed. Martindale: The Extra Pharmacopoeia. 30th ed. London, England: Pharmaceutical Press; 1993:1192.
4. Hardman JG, Limbird LE. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1996:1411-1437.
5. McEvoy GK, ed. AHFS Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists; 2012:3144.
6. Lacy C, Armstrong, LL, Goldman MP, Lance LL, eds. Drug Information Handbook. 13th ed. Hudson, OH: Lexi-Comp, Inc; 2005:549-553.
7. Heljo P. Saccharin. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:693-695.
8. Hapgood KP. Colloidal silicon dioxide. In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:198-201.