Published February 15, 2024 CARDIOVASCULAR Captopril 1 mg/mL Oral Solution Amanda Ye, RPh, PharmDMedical Director–Health Professional Digital EducationStaten Island, New York US Pharm. 2024;49(2):59-60.Method of Preparation: Calculate the amount of each ingredient required for the total volume to be prepared. Remove trademark imprint from the captopril tablets with a paper towel dampened with Alcohol, USP; allow tablets to air-dry for a few minutes. Triturate captopril tablets to a fine powder in a mortar and pestle. Incorporate a minimal amount of water into the powder and mix well. Gradually add water geometrically, continuing to mix until the blend is uniform and well distributed. Transfer the mixture to a graduate; rinse mortar and pestle with additional water and add the rinse to the graduate. Add the ascorbic acid tablet to the mixture and let it dissolve. Bring the final volume to 100 mL with additional water. Stir well. Transfer contents to an amber glass dispensing bottle.Use: Captopril oral solution has been used to treat conditions such as hypertension and heart failure in adults and children.Packaging: Package in a tight, light-resistant amber glass container. Store at controlled refrigerated temperature.Labeling: Keep refrigerated. Protect from light. Shake well. Discard after ____ [time period].Stability: The USP default beyond-use date for preserved aqueous oral liquids is 35 days. However, according to captopril stability studies, this formulation is stable for 14 days at controlled room temperature and for 56 days when refrigerated.1-3Quality 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) all constitute examples of quality-control assessments.4Discussion: Captopril, a competitive angiotensin-converting enzyme (ACE) inhibitor, is pivotal in blocking the conversion of angiotensin I to angiotensin II. The diminished plasma angiotensin II and heightened plasma renin activity resulting from ACE inhibition is driven by the loss of negative feedback on renin release stemming from reduced angiotensin II. This decline in angiotensin II leads to decreased aldosterone secretion, potentially causing modest increases in serum potassium and the loss of sodium and fluid. Captopril’s antihypertensive effects persist longer than the observable inhibition of circulating ACE. The blood pressure (BP) reduction achieved with captopril use may be progressive, necessitating several weeks of therapy for maximum therapeutic effect. Furthermore, the BP-lowering effects of captopril and thiazide-type diuretics are additive. Captopril is also used in the treatment of heart failure, left ventricular dysfunction post myocardial infarction, and diabetic nephropathy.5Captopril (Capoten, 1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline, MW 217.29) is a white to off-white crystalline powder with a faintly sulfurous odor. Captopril is soluble in water (approximately 160 mg/mL), methanol, and ethanol and is sparingly soluble in chloroform and ethyl acetate. Captopril is available commercially as scored tablets in potencies of 12.5 mg, 25 mg, 50 mg, and 100 mg. Inactive ingredients used in captopril include microcrystalline cellulose, cornstarch, lactose, and stearic acid.5Ascorbic acid (L-ascorbic acid, vitamin C, C6H8O6, MW 176.12) is an antioxidant that is available as a white or slightly yellow powder or crystals. In pharmaceutical formulations, ascorbic acid is used in concentrations of 0.01% to 0.1% w/v. Among its other uses are pH adjustment in injectable solutions and supplementation in oral liquids. Ascorbic acid is freely soluble in water at a ratio of 1:3 and sparingly soluble in alcohol at a ratio of 1:40. Exposure to light causes ascorbic acid to gradually darken.1,6Purified water is water that has been filtered via distillation, ion exchange, reverse osmosis, or other suitable process. It is miscible with most polar solvents and is chemically stable in all physical states.7REFERENCES1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; September 2022.2. Nahata MC, Morosco RS, Hipple TF. Stability of captopril in liquid containing ascorbic acid or sodium ascorbate. Am J Hosp Pharm. 1994;51(13):1707-1708.3. Nahata MC, Morosco RS, Hipple TF. Stability of captopril in three liquid dosage forms. Am J Hosp Pharm. 1994;51(1):95-96.4. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.5. Capoten (captopril) product information. Spring Valley, NY: Par Pharmaceuticals, Inc; June 2012.6. Kibbe AH. Ascorbic acid. In: Sheskey PJ, Hancock BC, Moss GP, Goldfarb DJ, eds. Handbook of Pharmaceutical Excipients. 9th ed. London, England: Pharmaceutical Press; 2020:116-119.7. Dubash D, Shah U. Water. In: Sheskey PJ, Cook WG, Cable CG, eds. Handbook of Pharmaceutical Excipients. 8th ed. Washington, DC: American Pharmaceutical Association; 2017:1012-1016.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.To comment on this article, contact rdavidson@uspharmacist.com.