Bi-Est 80/20 Cream

US Pharm. 2023;48(9):59-60.

Method of Preparation: Calculate the required quantity of each ingredient for the total amount to be prepared. Accurately weigh the estriol (E₃) and estradiol (E₂). Combine the E₃, E₂, and a few drops of ethoxydiglycol; then mix, dispersing evenly, until a smooth paste is formed. Geometrically, incorporate the HRT Cream Base to final weight and mix to form a homogenous cream. Package and label.

Use: This formulation has been used in hormone replacement therapy (HRT) to alleviate menopausal symptoms such as hot flashes, vaginal dryness, and mood fluctuations.

Packaging: Package in a tight, light-resistant container.

Labeling: Keep out of reach of children. Use only as directed. Store in a cool, dry place. Avoid direct sunlight. Discard after _____ [time period].¹

Stability: The USP default beyond-use date for this preparation is up to 180 days.²

Quality Control: Weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth) are all examples of quality-control assessments).³

Discussion: Bi-Est contains two bioidentical estrogens: E₃ and E₂. Its broad range of delivery methods, such as capsules, troches, creams, and suppositories, enables it to be customized according to patient preference and therapeutic requirements. The most common Bi-Est dosage strength is an 80:20 ratio (E₃ 80%, E₂ 20%). Adverse effects associated with this bioidentical hormone cream vary based on the formulation and dosage. Common adverse effects of Bi-Est include fatigue, skin changes, headache, breast tenderness, and nausea.^2,4

E₃ (C₁₈H₂₄O₃, MW 288.4) is a natural estrogen and a metabolite of E₂. Although on its own it lacks sufficient potency to alleviate menopausal symptoms, the combination of E₃ with E₂ enhances therapeutic efficacy. E₃ occurs as a crystalline powder that has limited solubility in water but is soluble in alcohol and vegetable oils. E₃’s interaction with E₂ and estrone involves reversible oxidation, and its systemic bioavailability via vaginal administration is superior to that for oral delivery.^5,6

E₂ (oestradiol, beta-estradiol, C₁₈H₂₄O₂, MW 272.38) occurs as white or creamy-white hygroscopic crystals or as a crystalline powder. It has limited solubility in aqueous environments, and it is soluble in alcohol and sparingly soluble in vegetable oils. E₂ should be stored in an airtight container at controlled ambient temperature and safeguarded against exposure to light. E₂ is commercially available as oral tablets, injections, vaginal rings, and other forms. On its own, E₂ has low oral bioavailability. Transdermal E₂ avoids first-pass metabolic effects that reduce bioavailability.⁵

Ethoxydiglycol (CH₂OHCH₂OCH₂CH₂OC₂H₅, C₆H₁₄O₃, MW 134.20) is also known as diethylene glycol monoethyl ether, diethylene glycol ethyl ether, transcutol, and carbitol. It is a colorless liquid with a mild odor, and it has a density of 1.0272. Ethoxydiglycol is a hygroscopic organic solvent that can be mixed with water and other organic solvents. As a solvent, ethoxydiglycol improves the solubility and permeability of active ingredients, and it is also used as a solubilizer and a cosurfactant. Ethoxydiglycol is nonirritating and nonpenetrating when applied to human skin.⁷

HRT Cream Base is a smooth, odorless, and white to off-white cream. It is a vanishing oil-in-water emulsion that has moisturizing and penetration-enhancing capabilities. HRT Cream Base has a pH range of 5.60 to 7.25 and a specific gravity of 0.95 to 1.10.⁸ It has minimal solubility in cold water. HRT Cream Base is free of alcohol, petrolatum, and oil. Beyond its role as a hormone carrier, HRT Cream Base is extremely well suited for dermatologic applications, and its absorbency complements lipophilic drugs.

REFERENCES

1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; September 2022.
2. Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause. 2004;11:356-367.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Compounded bioidentical hormone preparations. In: Jackson LM, Parker RM, Mattison DR, eds. The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. Washington, DC: National Academies Press; 2020.
5. Lacy C, Armstrong LL, Ingrim NB, Lance LL. Drug Information Handbook. 4th ed. Hudson, OH: Lexi-Comp, Inc; 1996:445-447.
6. Reynolds JE, ed. Martindale: The Extra Pharmacopoeia. 30th ed. London, England: Pharmaceutical Press; 1993:1192.
7. Ash M, Ash I. Handbook of Pharmaceutical Additives. Brookfield, VT: Gower Publishing Ltd; 1995:484.
8. HRT Cream Base product information. Plattsburgh, NY: Medisca.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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