US Pharm. 2013;38(2):36-37.
Method of Preparation: Calculate the required quantity of each ingredient for the total amount to be prepared. Count out the required number of tablets. In a suitable mortar, pulverize the tablets to a fine powder. Add a small quantity of Ora-Plus and mix to form a smooth paste. Geometrically, add the remainder of the Ora-Plus and mix well. Add the Ora-Sweet to volume and mix well. Package and label.
Use: Lisinopril oral liquid has been used in the treatment of hypertension or congestive heart failure in pediatric patients.
Packaging: Package in tight containers.1
Labeling: Keep out of reach of children. Use only as directed. Shake well.
Stability: A beyond-use date of 90 days is appropriate for this preparation.1,2
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).3
Discussion: Lisinopril is used for the treatment of hypertension or congestive heart failure in pediatric patients. Infants and small children who require lisinopril usually need a liquid dosage form, as presented above.
Lisinopril (Prinivil, Zestril, C21H31N3O5.2H2O, MW 441.52) is an ACE inhibitor, cardiovascular agent, and renin-angiotensin-aldosterone system inhibitor. It is used alone or in combination with other classes of antihypertensive agents in the management of mild-to-severe hypertension. Lisinopril occurs as a white, odorless, crystalline powder that melts at about 160°C with decomposition. It is soluble in water (97 mg/mL) and practically insoluble in alcohol (<0.1 mg/mL). Lisinopril dihydrate 2.72 mg is equivalent to lisinopril 2.5 mg.1
In addition to the Ora-Plus–Ora-Sweet combination, the stability study referenced also included methylcellulose 1% preserved–simple syrup NF (1:13) as a vehicle studied at both 4°C and 25°C. The methylcellulose 1% solution consisted of methylcellulose 4,000 cps 10 g, methylparaben 200 mg, propylparaben 100 mg, and sufficient purified water to make 1,000 mL. The preparation was compounded by mixing the comminuted lisinopril tablets (100 mg) with 7.7 mL of methylcellulose 1% preserved solution with sufficient simple syrup to volume. The methylcellulose–simple syrup combinations were stable for 91 days at 4°C, but for only 56 days at 25°C. The pH value of about 4.8 for the Ora-Plus–Ora-Sweet combinations and the pH value of 6.7 for the methylcellulose–syrup combinations did not change during the study.2
Lisinopril is commercially available in strengths of 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, and 40 mg; brand names include Zestril and Prinivil. Prinivil tablets also contain calcium phosphate, mannitol, magnesium stearate, and starch. The 10-mg and 20-mg tablets also contain iron oxide. The 2.5-mg Zestril tablets also contain calcium phosphate, magnesium stearate, mannitol, and starch. The 5-mg, 10-mg, 20-mg, and 30-mg tablets contain calcium phosphate, magnesium stearate, mannitol, red ferric oxide, and starch; the 40-mg tablets contain calcium phosphate, magnesium stearate, mannitol, starch, and yellow ferric oxide.4,5
Ora-Plus is an oral suspending vehicle that accepts dilution of up to 50% or more with water, flavoring agents, or syrups while still retaining its suspending properties. It has a pH of approximately 4.2 and an osmolality of about 230 mOsm/kg. Ora-Plus is a thixotropic vehicle with a viscosity of approximately 1,000 cps at 25°C. It contains purified water, microcrystalline cellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, sodium phosphate, and citric acid as buffering agents; simethicone as an antifoaming agent; and potassium sorbate and methylparaben as preservatives.6
Ora-Sweet syrup vehicle is a flavoring vehicle for oral extemporaneous preparations. It is flavored with a citrus-berry flavor blend and contains glycerin and sorbitol to prevent cap lock, a problem associated with many syrups. Ora-Sweet is buffered to a pH of approximately 4.2 and has an osmolality of about 3,240 mOsm/kg. It contains purified water, sucrose, glycerin, sorbitol (5%), flavoring, sodium phosphate, and citric acid as buffering agents, and potassium sorbate and methylparaben as preservatives.7
REFERENCES
1. U.S. Pharmacopeia 35/National Formulary 30. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2012:1126,3695-3697.
2. Nahata MC, Morosco RS. Stability of lisinopril in two liquid dosage forms. Ann Pharmacother. 2004;38:396-399.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Physicians’ Desk Reference. 67th ed. Montvale, NJ: PDR Network; 2013:1674-1678.
5. Zestril (lisinopril) product information. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2012.
6. Ora-Plus product information. Minneapolis, MN: Paddock Laboratories, Inc; 2010.
7. Ora-Sweet product information. Minneapolis, MN: Paddock Laboratories, Inc; 2010.
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