Valcyte

METHOD OF PREPARATION

1. Calculate the required quantity of each ingredient for the total amount to be prepared.

2. Accurately weigh and/or measure each ingredient.

3. If tablets are used, pulverize the tablets to a fine powder, or use bulk valganciclovir hydrochloride powder.

4. Slowly add the Ora-Plus and mix, forming a smooth paste and then a uniform suspension.

5. Slowly add the Ora-Sweet to volume and mix well.

6. Package and label.

PACKAGING

Package in tight, light-resistant containers.

LABELING

Keep out of reach of children. Use only as directed. Shake well before taking. Refrigerate.

STABILITY

A beyond-use date of 35 days can be used for this preparation.1,2

USE

Valganciclovir hydrochloride oral liquid is used in the treatment of cytomegalovirus retinitis and in the prevention of cytomegalovirus disease in transplant recipients.3

QUALITY CONTROL

Quality-control assessment can include weight/volume, pH (pH 3.8), specific gravity, active drug assay, color, clarity, rheological properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth)/

DISCUSSION

Valganciclovir, a prodrug of ganciclovir, is the L-valyl ester of ganciclovir, which does not exert activity until converted by the intestinal and hepatic esterases to ganciclovir and ultimately to the active form, ganciclovir triphosphate. Valganciclovir has greater gastrointestinal absorption and yields higher plasma ganciclovir concentrations than oral ganciclovir, levels comparable to those achieved with intravenous ganciclovir. Valganciclovir results in approximately 10-fold greater ganciclovir bioavailability than ganciclovir itself when both are administered orally.3

Valganciclovir hydrochloride (C^sub 14^H^sub 22^N^sub 6^O^sub 5^.HCl, MW 390.82, Valcyte) occurs as a white to off-white crystalline powder. It has a solubility of 70 mg/mL in water at 25°C at a pH of 7.0, and an n-octanol/water partition coefficient of 0.0095 at pH 7.0. The pK, for valganciclovir is 7.6. The Valcyte 450-mg tablets also contain microcrystalline cellulose, povidone K-30, crospovidone, and stearic acid. The film coating contains Opadry Pink.5

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 thixotropic, 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 is a flavoring vehicle for oral extemporaneous preparations. It has a citrus-berry flavor blend and contains glycerin and sorbitol to prevent "cap-lock" problems 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 water, sucrose, glycerin, sorbitol (5%), flavoring, sodium phosphate and citric acid as buffering agents, and potassium sorbate and methylparaben as preservatives.7

References

1. Henkin CC, Griener JC, Ten Eick AP. Stability of valganciclovir in extemporaneously compounded liquid formulations. Am J Health Syst Pharm 2003; 60(7): 687-690.

2. US Pharmacopeial Convention, Inc. USP-Pharmacists' Pharmacopeia. Rockville, MD: US Pharmacopeial Convention, Inc.; 2005: 362, 408-431.

3. McEvoy GK, ed. AHFS Drug Information-2005. Bethesda, MD: American Society of Health-Systems Pharmacists; 2005: 816-817.

4. Allen LV Jr. Standard operating procedure for quality assessment of oral and topical liquids. IJPC 1999; 3(2): 146-147.

5. [No author listed.] Physicians' Desk Reference. 58th ed. Montvale, NJ: Thomson PDR; 2004: 2970-2973.

6. Ora-Plus [product information]. Minneapolis, MN: Paddock Laboratories, Inc.

7. Ora-Sweet [product information]. Minneapolis, MN; Paddock Laboratories, Inc.

Copyright International Journal of Pharmaceutical Compounding Nov/Dec 2005
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