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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