Lisinopril is commercially available in 2.5-mg, 5-mg, 10-mg, 20-mg,
`30-mg, and 40-mg strengths; brand names include Zestril and Prini-
`vil. Prinivil tablets also contain calcium phosphate, mannitol, mag-
`nesium stearate, and starch. The 10-mg, 20-mg, and 40-mg tablets
`also contain iron oxide. Zestril tablets also contain calcium phos-
`phate, magnesium stearate, mannitol, and starch in the 2.5-mg tab-
`lets. 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
`Ora-Plus is an oral suspending vehicle that accepts dilution of up to
`50% or more with water, flavoring agents, or syrups and still retains
`its suspending properties. It has a pH of approximately 4.2 and an
`osmolality of about 230 mOsm/kg. It 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, and carrageenan; sodium phosphate and citric acid as
`buffering agents; simethicone as an antifoaming agent; and potas-
`sium sorbate and methylparaben as preservatives.5
`Ora-Sweet syrup is a flavoring vehicle for oral extemporaneous prep-
`arations. It is flavored with a citrus-berry flavor blend and contains
`glycerin and sorbitol to prevent “cap-lock,” a problem associated
`with many syrups. It is buffered to a pH of approximately 4.2 and
`has an osmolality of about 3,240 mOsm/kg. It contains purified wa-
`ter, sucrose, glycerin, sorbitol (5%), and flavoring; sodium phosphate
`and citric acid as buffering agents; and potassium sorbate and methyl-
`paraben as preservatives.6
`References
`1. United States Pharmacopeial Convention, Inc. USP Pharmacists’ Pharmacopeia.
`Rockville, MD: US Pharmacopeial Convention, Inc.; 2005: 198, 408–413, 693.
`2. Nahata MC, Morosco RS. Stability of lisinopril in two liquid dosage forms.
`Ann Pharmacother2004; 38(3): 396–399.
`3. Allen LV Jr. Standard operating procedure for quality assessment of oral and
`topical liquids. IJPC1999; 3(2): 146–147.
`[No author listed.] Physicians’ Desk Reference.60th ed. Montvale, NJ: Thomson
`PDR; 2006: 704, 2029.
`5. Ora-Plus [product information]. Minneapolis, MN: Paddock Laboratories, Inc.
`6. Ora-Sweet [product information]. Minneapolis, MN: Paddock Laboratories, Inc.
`
`4.
`
`F O R M U L A T I O N S
`
`Lisinopril 1-mg/mL Oral Liquid
`
`Rx
`
`For 100 mL
`Lisinopril tablets
`Ora-Plus
`Ora-Sweet
`
`100 mg
`50 mL
`100 mL
`
`qs
`
`METHOD OF PREPARATION
`1. Calculate the required quantity of each ingredient for the total
`amount to be prepared.
`2. Count out the required number of tablets.
`3. Pulverize the tablets to a fine powder in a suitable mortar.
`4. Add a small quantity of Ora-Plus and mix to form a smooth paste.
`5. Add the remainder of the Ora-Plus geometrically and mix well.
`6. Add the Ora-Sweet to volume and mix well.
`7. Package and label.
`PACKAGING
`Package in tight, light-resistant 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
`USE
`Lisinopril oral liquid has been used in the treatment of hyperten-
`sion or congestive heart failure in children.
`QUALITY CONTROL
`Quality-control assessment can include weight/volume, pH, specific
`gravity, active drug assay, color, rheological properties/pourability,
`physical observation, and physical stability (discoloration, foreign
`materials, gas formation, mold growth).3
`DISCUSSION
`Lisinopril (C21H31N3O5.2H2O, MW 441.52) is an angiotensin-
`converting enzyme (ACE) inhibitor, which acts as an inhibitor of the
`renin-angiotensin-aldosterone system in the treatment of cardiovas-
`cular disorders. It is used alone or in combination with other classes
`of antihypertensive agents in the management of mild to severe hy-
`pertension. It occurs as a white, crystalline powder that melts at
`about 160°C with decomposition. It is soluble in water and practi-
`cally insoluble in alcohol.1
`In a published stability study, lisinopril was investigated in two vehi-
`cles: a combination of Ora-Plus and Ora-Sweet and a combination
`of methylcellulose 1% and Simple Syrup NF (1:13) at both 4° and
`25°C. Lisinopril was stable in the methylcellulose-simple syrup com-
`bination for 91 days at 4°C but for only 56 days at 25°C. The pH
`values of about 4.8 for the Ora-Plus:Ora-Sweet combination and
`6.7 for the methylcellulose:syrup combination did not change dur-
`ing the study.2
`
`302 International Journal of Pharmaceutical Compounding
`Vol. 10 No. 4 July/August 2006
`
`Flat Line Capital Exhibit 1011
`Page 1 of 1
`
`KVK-Tech, Flat Line Capital Exhibit 1011
`Page 1
`
`