US Pharm. 2022;47(4):58-59.
Method of Preparation: Calculate the required quantity of each ingredient for the total amount to be prepared. Accurately weigh or measure each ingredient. Empty the required number of molnupiravir capsules into a mortar. Pulverize the powder to a fine state of subdivision. Add sufficient Ora-Sweet SF to form a smooth paste. Geometrically, add sufficient quantities of Ora-Sweet SF to final volume, with thorough mixing after each addition. Package and label.
Use: Molnupiravir is authorized for emergency use in the treatment of coronavirus disease 2019 (COVID-19) in certain adult patients.
Packaging: Package in tight, light-resistant containers.
Labeling: Keep out of reach of children. Discard after ____ [time period]. Shake well. Refrigerate.
Stability: Check with the state board of pharmacy for any updates on determining beyond-use dates. A beyond-use date of 14 days when stored in a refrigerator may be used for this preparation.1
Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, physical stability (discoloration, foreign materials, gas formation, mold growth), and preservative-effectiveness test.2,3
Discussion: Molnupiravir (C13H19N3O7, MW 329.3) is a nucleoside analogue that inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication by viral mutagenesis. It is the 5´-isobutyrate ester of the ribonucleoside analogue N4-hydroxycytidine. The chemical name for molnupiravir is {(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]oxolan-2-yl}methyl 2-methylpropanoate. Molnupiravir occurs as a white to off-white powder that is soluble in water. The drug will dissolve in the vehicle used in the above formula. The excipients may not dissolve, but they can be easily suspended with gentle shaking in this suspension. Each immediate-release molnupiravir capsule for oral use contains 200 mg of molnupiravir and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, and purified water. The capsule shell is made of hypromellose, red iron oxide, and titanium dioxide. The capsule is printed with white ink made of butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, strong ammonia solution, and titanium dioxide.4
Molnupiravir is a prodrug with antiviral activity against SARS-CoV-2. The dosage of molnupiravir is 800 mg, or four of the 200-mg capsules taken twice daily. This can be problematic for some patients with swallowing difficulties. A dose of 10 mL, or 2 teaspoons of the above preparation, would provide the recommended molnupiravir dosage of 800 mg and is much easier to swallow than the four capsules.5
Other drugs of the same general class with liquid dosage forms, either compounded or manufactured, include oseltamivir (Tamiflu), which can be compounded, and the ritonavir component of Paxlovid (nirmatrelvir/ritonavir). Ritonavir 80 mg/mL oral solution contains a large amount of alcohol. Because of this, a toddler or young child can become sick from accidentally drinking more than the recommended dose of ritonavir.4
Ora-Sweet SF syrup vehicle is a flavoring vehicle for oral extemporaneous preparations. It is a sugar-free, alcohol-free syrup flavored with a citrus–berry flavor blend. Ora-Sweet SF is buffered to a pH of approximately 4.2, and it may be used alone or in combination with other vehicles. Ora-Sweet SF will tolerate a dilution to 50% with dissolved actives in water or suspending agents while still retaining an acceptable taste. It has an osmolality of 2,150 mOsm/kg. Ora-Sweet SF contains water, sodium saccharin, xanthan gum, glycerin, sorbitol, citric acid, and sodium citrate as buffers; methylparaben, propylparaben, and potassium sorbate as preservatives; and flavoring agents.6
Other similar oral liquid vehicles are available and may be considered for use. Additional suspending agents should not be necessary because the capsule excipients contain croscarmellose sodium, hydroxypropyl cellulose, and microcrystalline cellulose, which may add to the viscosity of the vehicle.
REFERENCES
1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; March 2022.
2. Allen LV Jr. Summary of quality-control testing for sterile and nonsterile compounded preparations, part 1: physical and chemical testing. IJPC. 2019;23(3):211-216.
3. Allen LV Jr. Summary of quality-control testing for sterile and nonsterile compounded preparations, part 2: microbiological testing. IJPC. 2019;23(4):299-303.
4. Lagevrio (molnupiravir) Emergency Use Authorization package insert. Whitehouse Station, NJ: Merck & Co, Inc; February 2022.
5. ClinicalInfo Drug Database. Ritonavir. https://clinicalinfo.hiv.gov/en/drugs/ritonavir/patient. Accessed March 12, 2022.
6. Ora-Sweet SF product information. Allegan, MI: Perrigo; 2019.
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.
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